Oral Cladribine in Early Multiple Sclerosis (MS) | NCT00725985 | Trialant
NCT00725985
Sponsor
EMD Serono Research & Development Institute, Inc.
Status
Completed
Last Update Posted
Mar 22, 2021Actual
Enrollment
617Actual
Phase
Phase 3
Conditions
Multiple Sclerosis
Interventions
Cladribine
Placebo
Rebif® new formulation (RNF)
Countries
United States
Argentina
Austria
Belgium
Bosnia and Herzegovina
Bulgaria
Canada
Croatia
Czechia
Estonia
Finland
France
Georgia
Germany
India
Italy
Lebanon
North Macedonia
Norway
Poland
Portugal
Romania
Russia
Serbia
Singapore
South Korea
Spain
Sweden
Taiwan
Thailand
Turkey (Türkiye)
Ukraine
United Arab Emirates
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT00725985
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
28821
Secondary IDs
Not provided
Brief Title
Oral Cladribine in Early Multiple Sclerosis (MS)
Official Title
A Phase III, Randomized, Double-blind, Placebo-controlled, Multi-center Clinical Trial of Oral Cladribine in Subjects With a First Clinical Event at High Risk of Converting to MS
Acronym
ORACLE MS
Organization
EMD SeronoINDUSTRY
Status Module
Record Verification Date
Feb 2021
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Dec 31, 2008Actual
Primary Completion Date
Jul 31, 2011Actual
Completion Date
Apr 30, 2012Actual
First Submitted Date
Jul 30, 2008
First Submission Date that Met QC Criteria
Jul 30, 2008
First Posted Date
Jul 31, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Jun 11, 2013
Results First Submitted that Met QC Criteria
Aug 2, 2013
Results First Posted Date
Oct 10, 2013Estimated
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Feb 24, 2021
Last Update Posted Date
Mar 22, 2021Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
EMD Serono Research & Development Institute, Inc.INDUSTRY
Collaborators
Not provided
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
A randomized, double-blind, clinical trial to assess the safety and efficacy of two doses of oral cladribine versus placebo in participants who had a first clinical demyelinating event (clinically isolated syndrome). Participants in either the cladribine or placebo group may also enter treatment periods with open-label interferon-beta or open-label cladribine depending upon the disease status. The primary objective of this study is to evaluate the effect of two dosage regimens of oral cladribine versus placebo on the time to conversion to multiple sclerosis (MS) (from randomization) according to the Poser criteria in participants with first clinical demyelinating event at high risk of converting to MS.
Detailed Description
This will be a randomized, double blind, three-arm, placebo-controlled, multi-center trial to evaluate the safety and efficacy of oral cladribine versus placebo in the treatment of participants who have sustained a first clinical demyelinating event within 75 days prior to the Screening. Participants must have a minimum of 2 clinically silent lesions on the Screening magnetic resonance imaging (MRI).
The study will include a pre-study evaluation period (Screening period: between 10 and 28 days prior to the start of treatment with blinded study medication (oral cladribine or placebo).
Depending upon the clinical course of their MS, participants will then proceed from the ITP to either the Maintenance Treatment Period (with open-label interferon-beta treatment) or LTFU period (with either open-label low-dose cladribine or no additional treatment (if no progression to MS has been noted after the initial treatment period). The single primary endpoint for the overall study, which will be determined during the ITP, is time to conversion to MS (from randomization), according to the Poser criteria.
For every participants, eligibility for study enrollment and entry into each of the study periods, and diagnosis of conversion to either McDonald MS or CDMS must be confirmed and approved by a Sponsor appointed study Adjudication Committee.
Conditions Module
Conditions
Multiple Sclerosis
Keywords
Clinically Isolated Syndrome (CIS)
Early MS
Multiple Sclerosis
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 3
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
617Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cladribine 5.25 mg/kg (ITP)
Experimental
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 milligrams per kilograms (mg/kg) during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Cladribine 3.5 mg/kg (ITP)
Experimental
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Placebo (ITP)
Placebo Comparator
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Drug: Placebo
Drug: Rebif® new formulation (RNF)
Cladribine 5.25 mg/kg, Rebif (OLMP)
Experimental
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Cladribine
Drug
Cladribine tablets were administered until CDMS conversion, whichever occur first.
Cladribine 3.5 mg/kg (ITP)
Cladribine 3.5 mg/kg, Rebif (LTFU)
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
ITP: Baseline up to Week 96
Secondary Outcomes
Measure
Description
Time Frame
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Male or female between 18 and 55 years old, inclusive
Weighed between 40 to 120 kilogram (kg), inclusive
Participant has experienced a single, first clinical event suggestive of MS within 75 days prior to the Screening visit, (clock starts 24 hours after onset). The event must be a new neurological abnormality present for at least 24 hours, either mono- or polysymptomatic
Participant has at least two clinically silent lesions on the T2-weighted MRI scan, at screening, with a size of at least 3 millimeter (mm), at least one of which is ovoid or periventricular or infratentorial on screening MRI
Participant has EDSS 0 - 5.0 at Screening
Participant has no medical history or evidence of latent tuberculosis infection (LTBI) or active tubercular disease, as evidenced by the Mantoux tuberculosis (TB) skin test or a comparable sensitive test according to local regulations/guidelines (if the Mantoux test is not available), and/or a chest X-ray
Participant has normal hematological parameters at Screening, as defined by the central laboratory that performed all the assessments
If female, she must:
be neither pregnant nor breast-feeding, nor attempting to conceive and
use a highly effective method of contraception throughout the entire duration of the study and for 90 days following completion of the last dose of study medication. A highly effective method of contraception is defined as those which result in a low failure rate (that is less than 1 percent per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices, sexual abstinence or vasectomized partner, or
be post-menopausal or surgically sterilized (Note: for Danish sites only, participants should use a hormonal contraceptive or intrauterine device for the duration of the trial)
Male participants must be willing to use contraception to avoid impregnating partners throughout the study, and for 90 days following the last dose of study medication
Be willing and able to comply with study procedures for the duration of the study
Participant has to provide written informed consent voluntarily, including, for United states of America (USA), participant authorization under Health Insurance Portability and Accountability Act (HIPAA), prior to any study-related procedure that is not part of normal medical care
Participant has refused any treatment already available for clinically isolated syndrome (CIS) such as interferons or glatiramer acetate, at the time of entry into the Initial Treatment Period of this study
Exclusion Criteria:
Participant has a diagnosis of MS (per McDonald criteria, 2005)
Participant has any other disease that could better explain the participant's signs and symptoms
Participant has complete transverse myelitis or bilateral optic neuritis
Participant using or has used any other approved MS disease modifying drug (DMD)
Participant has used any investigational drug or undergone an experimental procedure within 12 weeks prior to Study day 1
Participant received oral or systemic corticosteroids or adrenocorticotropic hormone (ACTH) within 30 days prior to screening MRI. The MRI had to be performed 30 days after the oral or systemic corticosteroids or ACTH treatment. In case this interfered with MRI timing the screening period could be extended accordingly.
Participant has abnormal total bilirubin, or aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase greater than 2.5 times the upper limit of normal
Participant suffered from current autoimmune disease other than MS
Participant suffered from psychiatric illness (including history of, or concurrent, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the participant or could affect compliance with the study protocol
Participant suffered from major medical illness such as cardiac (for example angina, congestive heart failure or arrhythmia), endocrinologic, hepatic, immunologic, metabolic, renal, pulmonary, gastrointestinal, dermatologic, or other major disease that would preclude the administration of oral cladribine
Participant has a history of seizures not adequately controlled by medications
Participant has a known allergy to cladribine, interferon-beta, the excipient(s) of the study medications, or to gadolinium- diethylenetriamine penta-acetic acid (DTPA)
Participant has any renal condition that would preclude the administration of gadolinium (for example acute or chronic severe renal insufficiency (glomerular filtration rate [GFR] less than 30 milliliter per minute per 1.73 square meter [mL/min/1.73 m^2])
Participant has a history of chronic or clinically significant hematological abnormalities
Participant has a history of active or chronic infectious disease or any disease that compromises immune function (for example human immunodeficiency virus positive [HIV+], human T-lymphotrophic virus [HTLV-1], Lyme disease, latent tuberculosis infection [LTBI] or TB, insulin-dependent diabetes).
Participant has previously been screened in this study (signed an informed consent) and then withdrawn
Participant has received any immunomodulatory or immunosuppressive therapy) at any time prior to Study Day 1, including, but not limited to, the following products: any interferon, glatiramer acetate (Copolymer I), cyclophosphamide, cyclosporine, methotrexate, linomide, azathioprine, mitoxantrone, teriflunomide, laquinimod, cladribine, total lymphoid irradiation, anti-lymphocyte monoclonal antibody treatment (for example natalizumab, alemtuzumab/Campath, anti-cluster of differentiation 4 [CD4]), intravenous immunoglobulin G (IVIG), cytokines or anti-cytokine therapy
Participant has received experimental MS treatment
Participant has a history of alcohol or drug abuse
Participant has intolerance or any contraindication to both paracetamol (acetaminophen) and ibuprofen
Participant has inability to administer subcutaneous injections either by self or by caregiver
Participant has prior or current malignancy (with the exception of in situ basal or squamous cell skin cancer surgically removed without recurrence for at least five years)
Participant has a positive stool hemoccult test at Screening
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
55 Years
Standard Ages
Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Bettina Stubinski, MD
Merck Serono S.A., Geneva
Study Director
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Hope Research Institute Medical Plaza LLC Desert Hills
Phoenix
Arizona
United States
Multiple Sclerosis Center Drive, Neurology Suite 701
Oh J, Walker B, Giovannoni G, Jack D, Dangond F, Nolting A, Aldridge J, Lebson LA, Leist TP. Side effects that occurred early in people with multiple sclerosis during the first year of treatment with cladribine tablets: a plain language summary. Neurodegener Dis Manag. 2022 Feb 1;12(1):1-7. doi: 10.2217/nmt-2021-0041. Epub 2022 Jan 12.
A total of 617 participants were randomized for initial treatment period (ITP) and 616 participants received study drug.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Placebo, Rebif (OLMP)
Experimental
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Experimental
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Drug: Placebo
Cladribine 5.25 mg/kg, Rebif (LTFU)
Experimental
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Cladribine 3.5 mg/kg, Rebif (LTFU)
Experimental
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Drug: Cladribine
Drug: Rebif® new formulation (RNF)
Placebo, Rebif (LTFU)
Experimental
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Placebo matched to cladribine tablets were administered.
Placebo (ITP)
Placebo, Rebif (LTFU)
Placebo, Rebif (OLMP)
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Rebif® new formulation (RNF)
Drug
Participants who converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received RNF subcutaneously at a dose of 44 microgram (mcg) three times a week. Participants who converted to CDMS during long-term follow-up (LTFU) period, received RNF subcutaneously at a dose of 44 mcg three times a week.
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Baseline up to Week 96
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Time from Randomization up to 1217 days
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
Time from Randomization up to 1217 days
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
ITP: Baseline up to week 96
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
ITP: Baseline up to week 96
ITP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
ITP: Baseline, Week 96
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 24, 48, 72 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24 and 36
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 13, 24, 36 and 48
ITP: Changes From Baseline in Volume of T2 Lesions
Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
ITP: Baseline, Week 48 and 96
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
Baseline, Week 48
ITP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
ITP: Baseline, Week 48 and 96
OLMP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP: Baseline, Week 48 and 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline (Day 1)
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU: Baseline, Week 48
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
OLMP: Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
LTFU: Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
Baseline up to Week 48
ITP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
ITP: Baseline up to Week 96
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
OLMP: Baseline up to 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
LTFU: Baseline up to Week 48
ITP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
ITP: Baseline, Week 48 and 96
OLMP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
OLMP: Baseline, Week 48 and 96
OLMP: Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Baseline up to Week 96
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Baseline up to Week 48
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Baseline up to Week 48
OLMP: Annualized Relapse Rate
The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Baseline up to Week 96
OLMP: Percentage of Relapse-Free Participants
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
Baseline up to Week 96
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
ITP: Baseline up to Week 96
Newport Beach
California
United States
University of Colorado at Denver Health Sciences
Denver
Colorado
United States
Fort Collins Neurology
Fort Collins
Colorado
United States
MS Center of Brevard MIMA Centry Research Associates
Melbourne
Florida
United States
University of South Florida
Tampa
Florida
United States
MS Center of Atlanta
Atlanta
Georgia
United States
Bruce Hughes West Building
Des Moines
Iowa
United States
Michigan Neurology Associates
Clinton Township
Michigan
United States
Henry Ford Hospital
Detroit
Michigan
United States
University of Minnesota
Minneapolis
Minnesota
United States
Dennis Dietrich
Great Falls
Montana
United States
University of Medicine and Dentistry of New Jersey School of Neurology
Stratford
New Jersey
United States
Upstate Clinical Research LLC 3
Albany
New York
United States
Neurological Specialists of Long Island
Great Neck
New York
United States
Multiple Sclerosis Center of Northeastern NY
New York
New York
United States
Comprehensive MS Care Clinic at South Shore Multiple Sclerosis
Patchogue
New York
United States
Carolinas Medical Center
Charlotte
North Carolina
United States
Meritcare Neuroscience Center Neurology
Fargo
North Dakota
United States
University of Cincinnati
Cincinnati
Ohio
United States
MS Center of Oklahoma
Oklahoma City
Oklahoma
United States
Neurology and Sleep Medicine
Bethlehem
Pennsylvania
United States
Swedish Medical Center Cherry Hill
Seattle
Washington
United States
Neurology & Neurological Association of Tacoma
Tacoma
Washington
United States
Instituto Medico Rodriguez Alfici
Godoy Cruz
Argentina
Fundacion Rosarina de Neurorehabilitacion
Rosario
Argentina
Krankenhaus der Barmherzigen Brüder
Linz
Austria
Algemeen Ziekenhuis St Jan
Bruges
Belgium
Cliniques Universitaires St-Luc
Brussels
Belgium
Hopital Erasme
Brussels
Belgium
CHU de Liege - Domaine Universitaire du Sart Tilman,
Liège
Belgium
Clinical Center University of Sarajevo
Sarajevo
Bosnia and Herzegovina
Military Medical Academy- Sofia (MMA)
Pleven
Bulgaria
MBAL Rousse AD 1st
Rousse
Bulgaria
Central Clinic Hospital
Sofia
Bulgaria
Military Medical Academy
Sofia
Bulgaria
National Heart Hospital
Sofia
Bulgaria
Second MHAT
Sofia
Bulgaria
Tokuda Hospital
Sofia
Bulgaria
University Hospital St Naum
Sofia
Bulgaria
Medical Centre Centromed 2000
Veliko Tarnovo
Bulgaria
Ottawa General Hospital
Ottawa
Canada
General Hospital Varazdin
Varaždin
Croatia
University Hospital Zagreb
Zagreb
Croatia
Faculty Hospital Brno
Brno
Czechia
Neurological dept of Faculty
Hradec Králové
Czechia
Fakultní nemocnice s poliklinikou Ostrava
Ostrava
Czechia
Faculty Hospital Motol
Prague
Czechia
Klinika Vseobecne
Prague
Czechia
Nemocnice Teplice
Teplice
Czechia
East Tallinn Central Hospital
Tallinn
Estonia
West Tallinn Central Hospital
Tallinn
Estonia
HUS Hyvinkaa Central Hospital
Hyvinkää
Finland
OYKS Neurologian Klinikka
Oulu
Finland
Neurologian Klinikka Seinajoen Keskussairaala
Seinäjoki
Finland
Tampere University Hospital
Tampere
Finland
Turun Yliopistollinen Keskussairaala Rakennus 3 1
Turku
Finland
CHU de Lille
Lille
France
CHU de Nantes
Nantes
France
American Memorial Hospital
Reims
France
David Tatishvili Medical Center
Tbilisi
Georgia
Medical Center Health
Tbilisi
Georgia
S. Khechinashvili Tbilisi State Medical University
Tbilisi
Georgia
Universitaetsklinikum und Medizinische Fakultaet Heidelberg
Heidelberg
Germany
Philipps-Universitaet Marburg
Marburg
Germany
M S Ramaiah Medical College Hospital
Bangalore
Karnataka
India
St.John's Medical College and Hospital
Bangalore
Karnataka
India
Amrita Institute of Medical Sciences and Research
Kochi
Kerala
India
Kovai Medical Centre and Hospital
Coimbatore
India
Sanjay Gandhi Post Graduate Institute of Medical Sciences
Lucknow
India
Mallikatta Neuro and Research Centre
Mangalore
India
Ospedale Regionale Torrette
Ancona
Italy
Università de Bari
Bari
Italy
Ospedale Binaghi Centro Sclerosi Multipla
Cagliari
Italy
Azienda Ospedaliera Garibaldi
Catania
Italy
Dipartimento di Neuroscienze
Catania
Italy
Università G. D'Annunzio
Chieti
Italy
Ospedale San Antonio Abate
Gallarate
Italy
Universita degli Studi di Genova
Genova
Italy
Ospedale e casa di riposo P. Richiedei
Gussago
Italy
Ospedale San Raffaele
Milan
Italy
Dipartimento di Scienze Neurologiche
Naples
Italy
Azienda Sanitaria Ospedaliera San Luigi Gonzaga
Orbassano
Italy
Villa Sofia Hospital Azienda Ospedaliera Villa Sofia P.zza Salerno e Resuttana 1
Palermo
Italy
Istituto Neurologico C. Mondino
Pavia
Italy
Azienda Ospedaliera S. Camillo Forlanini
Roma
Italy
Azienda Ospedaliera Universitaria Policlinico Tor Vergata
Roma
Italy
Università di Roma La Sapienza
Roma
Italy
American University of Beirut
Beirut
Lebanon
Clinic of Neurology "Klinicki Centar"
Skopje
North Macedonia
Helse Bergen HF Kvinneklinikken Haukeland Universitetssykehus Jonas
Bergen
Norway
Regionsykehuset I Trondheim, Nevrologisk avd.
Trondheim
Norway
10 Wojskowy Szpital Kliniczny
Bydgoszcz
Poland
Wojewodzki Szpital Specjalistyczny im. M. Kopernika
Gdansk
Poland
Niepubliczny Zespol Opieki Zdrowotnej
Krakow
Poland
Medical Academy of Lodz
Lodz
Poland
Panstwowy Szpital Kliniczny
Lublin
Poland
Wojewodzki Szpital Specjalistyczny Oddział Neurologii z Pododdziałem Udarowym
Olsztyn
Poland
Medical Academy
Poznan
Poland
Medical Academy II
Warsaw
Poland
Medical Academy
Warsaw
Poland
Hospital Fernando da Fonseca
Amadora
Portugal
Hospitais da Universidade de Coimbra
Coimbra
Portugal
Hospital de Santa Maria
Lisbon
Portugal
Centro Hospitalar de Coimbra
S. Martinho Do Bispo
Portugal
"Dr. Carol Davilla" Military Clinical Hospital
Bucharest
Romania
Centrul Medical SANA
Bucharest
Romania
Spitalul Clinic Judetean Mures
Târgu Mureş
Romania
County Hospital Timisoara
Timișoara
Romania
Municipal Healthcare Institution "City Clinical Hospital #3"
Chelyabinsk
Russia
State Healthcare Institution "Kaluga Regional Hospital"
Kaluga
Russia
State Medical Institution "Republican Rehabilitation Clinic of Tatarstan Ministry of Health"
Kazan'
Russia
State Healthcare Institution "Kemerovo Regional Clinical Hospital"
Kemerovo
Russia
State Medical Institution " Jursk Regional Clinical Hospital"
Kursk
Russia
Moscow State Healthcare Institution City Clinical Hospital #11
Moscow
Russia
Non-State Healthcare Institution "Central Clinical Hospital #2 named after N.A. Semasko of Russian Railways"
Moscow
Russia
State Educational Institute of Higher Professional Education "I.M. Sechenov Moscow Medical Academy of Roszdrav" Russia based on A. Ya. Kozhevnikov Nervous Disease Clinic
Moscow
Russia
Municipal Treatment Prophylactic Institution "City Hospital #33"
Nizhny Novgorod
Russia
Federal State Institution " Siberian Reginal Medical Center of Roszdarv"
Novosibirsk
Russia
State institution Science Research Institute Clinical and Experimental Lymphology of Russian Academy of Medical Sciences
Novosibirsk
Russia
State Educational Institute of Higher Professional Education "Rostov State Medical University of Roszdrav"
Rostov-on-Don
Russia
State Healthcare Institution "Rostov Region Clinical Hospital"
Rostov-on-Don
Russia
Institute of Human Brain of Russian Academy of Science Dept. of Multiple Sclerosis
Saint Petersburg
Russia
International Clinic and Hospital, Neurology
Saint Petersburg
Russia
St. Petersburg State Healthcare Institution "Multifield City Hospital #2"
Saint Petersburg
Russia
State Educational Institution of Higher Professional Education "Military Medical Academy named after S. M. Korov of Dept of Defense of Russian Federation based on Clinic of Neurology of State Institution
Saint Petersburg
Russia
State Educational Institution of Higher Professional Education "Samara State Medical University of Roszdrav" on State Healthcare Institution "Samara Regional Clinical Hospital named after M. I. Kalinin"
Samara
Russia
State Educational Institution of Higher Professional Education "Saratov State Medical University of Roszdrav" based on Clincial Hosptial #3 of Saratov State Medical University
Saratov
Russia
Regional State Healthcare Institution "State Smolensk Region Clinical Hospital"
Smolensk
Russia
State Educational Institution of Higher Professional Education "Siberian State Medical University of Roszdrav"
Tomsk
Russia
Closed joint-stock society Medical sanitary unit "Nephtaynik" based the hospital
Tyumen
Russia
Vladimir Regional State Healthcare Institution "Regional Clinical Hospital"
Vladimir
Russia
Municipal Healthcare Institution "Yaroslavi Clinical Hospital #8"
Yaroslavl
Russia
State Healthcare Institution "Sverdlovsk Regional Clinical Hospital #1"
Yekaterinburg
Russia
Clinical Centre of Serbia
Belgrade
Serbia
Hospital for Prevention and Treatment of Cerebro-Vascular Diseases
Belgrade
Serbia
Clinical Centre Niš
Niš
Serbia
National Neuroscience Institute (TTSH Campus)
Singapore
Singapore
National Cancer Center, Department of Neurology,
Gyeonggi-do
South Korea
Department of Neurology, 50 Ilwon-dong, Gangnam-gu
Seoul
South Korea
Department of Neurology, Asan Medical Center, 388-1 Pungnap 2-dong, Songpa-gu
Seoul
South Korea
Seoul National University Hospital, Department of Neurology
Seoul
South Korea
Yonsei University Medical Center, Department of Neurology, Yonsei University Medical Center
Seoul
South Korea
Hospital Reina Sofia Cordoba
Córdoba
Spain
Hospital Universitario Nuestra Senora de la Candelaria
Santa Cruz de Tenerife
Spain
Sahlgrenskasjukhuset
Gothenburg
Sweden
Karolinska University Hospital
Stockholm
Sweden
Umea University Hospital
Umeå
Sweden
Taipei Veterans
Taipei
Taiwan
Chang Gung Medical Foundation- Linkou Branch No5
Taoyuan
Taiwan
Srinagarind Hospital
Khon Kaen
Thailand
Dokuz Eylul University
Izmir
Turkey (Türkiye)
Ondokuz Mayis Universitesi
Samsun
Turkey (Türkiye)
State Established "Institute of Neurology, Psychiatry and Narcology of the AMS of Ukraine", Depart of Neurinfections and Multiple Sclorosis
Kharkiv
Ukraine
Institue for Clinical Radiology of the State Establishment "Research Centre for Radiation Medicine of the AMS of Ukraino" Depart of Radiation Psychoneurology
Kiev
Ukraine
Vinnylsia Regional Psychoneurological Hosptial Named After O. I Yushchenko, Neurological Depart, Vinnytsia National Medical University Named After M. I. Pirogov, Chair of Neurology
Vinnitsa
Ukraine
Rashid Hospital
Dubai
United Arab Emirates
Kings College London
London
United Kingdom
Derived
Giovannoni G, Coyle PK, Vermersch P, Walker B, Aldridge J, Nolting A, Galazka A, Lemieux C, Leist TP. Integrated Lymphopenia Analysis in Younger and Older Patients With Multiple Sclerosis Treated With Cladribine Tablets. Front Immunol. 2021 Dec 24;12:763433. doi: 10.3389/fimmu.2021.763433. eCollection 2021.
Giovannoni G, Galazka A, Schick R, Leist T, Comi G, Montalban X, Damian D, Dangond F, Cook S. Pregnancy Outcomes During the Clinical Development Program of Cladribine in Multiple Sclerosis: An Integrated Analysis of Safety. Drug Saf. 2020 Jul;43(7):635-643. doi: 10.1007/s40264-020-00948-x.
Freedman MS, Leist TP, Comi G, Cree BA, Coyle PK, Hartung HP, Vermersch P, Damian D, Dangond F. The efficacy of cladribine tablets in CIS patients retrospectively assigned the diagnosis of MS using modern criteria: Results from the ORACLE-MS study. Mult Scler J Exp Transl Clin. 2017 Oct 9;3(4):2055217317732802. doi: 10.1177/2055217317732802. eCollection 2017 Oct-Dec.
Leist TP, Comi G, Cree BA, Coyle PK, Freedman MS, Hartung HP, Vermersch P, Casset-Semanaz F, Scaramozza M; oral cladribine for early MS (ORACLE MS) Study Group. Effect of oral cladribine on time to conversion to clinically definite multiple sclerosis in patients with a first demyelinating event (ORACLE MS): a phase 3 randomised trial. Lancet Neurol. 2014 Mar;13(3):257-67. doi: 10.1016/S1474-4422(14)70005-5. Epub 2014 Feb 4.
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
FG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
FG003
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
FG004
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
FG005
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
FG008
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
FG009
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
FG010
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
FG011
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
FG000205 subjects
FG001206 subjects
FG002206 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Treated
FG000204 subjects
FG001206 subjects
FG002206 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
COMPLETED
FG000104 subjects
FG001131 subjects
FG002104 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
NOT COMPLETED
FG000101 subjects
FG00175 subjects
FG002102 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Type
Comment
Reasons
Adverse Event
FG00020 subjects
FG00110 subjects
FG0025 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0022 subjects
FG0030 subjects
FG004
Randomized but not treated
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Converted to CDMS
FG00030 subjects
FG00127 subjects
FG00271 subjects
FG0030 subjects
FG004
Other
FG00050 subjects
FG00138 subjects
FG00224 subjects
FG0030 subjects
FG004
OLMP (Up to 96 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00324 subjects
FG00425 subjects
FG00560 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0036 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00318 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
LTFU (Cladribine Treatment) (48 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0069 subjects
FG0079 subjects
FG00817 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
LTFU (No Cladribine) (48 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG00934 subjects
FG01036 subjects
FG01114 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Type
Comment
Reasons
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cladribine 5.25 mg/kg
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.
BG001
Cladribine 3.5 mg/kg
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.
BG002
Placebo
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first. Participants who converted to CDMS during ITP entered OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Participants who did not convert to CDMS during ITP, entered in LTFU period. Participants who converted to McDonald MS during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any study treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period.
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000204
BG001206
BG002206
BG003616
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00031.9± 8.8
BG00131.7± 9.2
BG00232.2± 8.2
BG003
Age, Customized
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Greater than or equal to 30 years
BG000111
BG001110
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG000132
BG001130
BG002
Expanded disability status scale (EDSS) score
Expanded disability status scale (EDSS) assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated.
Mean
Standard Deviation
units on scale
Title
Denominators
Categories
Title
Measurements
BG0001.6± 0.9
BG001
Number of Time Constant 1 (T1) Gadolinium Enhanced (GD+) lesions
Mean
Standard Deviation
lesions
Title
Denominators
Categories
Title
Measurements
BG0001.9± 5.8
BG0011.5± 4.5
BG002
Number of T2 Lesions
Mean
Standard Deviation
lesions
Title
Denominators
Categories
Title
Measurements
BG00029.7± 29.6
BG00126.8± 28.3
BG002
Time from First Demyelinating Event to Randomization
Monofocal- Neurological signs and symptoms can be explained by only 1 single location; Multifocal- Neurological signs and symptoms can not be explained by only 1 single location.
Count of Participants
Participants
Title
Denominators
Categories
Monofocal
Title
Measurements
BG000108
BG001
Number of participants Using Steroid Treatment
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG000133
BG001131
BG002
Number of Participants with Time Constant 1 (T1) Gd-enhanced Lesions
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
BG00090
BG00174
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
ITP: Time to Clinically Definite Multiple Sclerosis (CDMS) Conversion Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With CDMS
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to Multiple Sclerosis [MS]) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. Kaplan-Meier estimates were provided for of the cumulative (cum.) percentage (%) of participants with CDMS over time. The probability of patients remaining event-free over time (from randomization) in each of the three treatment groups was displayed in the form of survival curves estimated using the non-parametric Kaplan-Meier method.
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Cum. % of participants with CDMS
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00015.8
OG00114.0
OG00237.8
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
two-sided Wald test
<0.0001
The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
Hazard Ratio (HR)
0.381
2-Sided
95
0.248
0.584
Superiority or Other (legacy)
OG001
OG002
two-sided Wald test
Secondary
ITP: Time to Develop Multiple Sclerosis (MS) Conversion According to the Revised McDonald Criteria (2005) Represented by Kaplan-Meier Estimates of the Cumulative Percentage of Participants With McDonald MS
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI. Dissemination in space is established by the presence of any 3 of the following: 1 Gd+ lesion or 9 T2 bright lesions if there is no enhancement; greater than or equal to 1 infratentorial lesion; greater than or equal to 1 juxtacortical lesion; greater than or equal to 3 periventricular lesions. Kaplan-Meier estimates were provided for the cum. percentage (%) of participants with McDonald MS over time.
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Cum. % of participants with McDonald MS
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Secondary
ITP: Number of Combined Unique Active (CUA) Lesions, New or Enlarging Time Constant 2 (T2) Lesions, and New or Persisting Time Constant 1 (T1) Gadolinium Enhanced (Gd+) Lesions Per Participant Per Scan
Number of CUA lesions, new or enlarging T2 lesions, and new or persisting T1 Gd+ lesions were measured by using magnetic resonance imaging (MRI) scans.
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Secondary
OLMP: Time to 3 Month Confirmed Expanded Disability Status Scale (EDSS) Progression From Randomization Represented by Kaplan-Meier Estimates of Probability of Disability Progression
EDSS progression is based on a standardized neurological exam and focuses on symptoms that commonly occur in Multiple Sclerosis (MS). Overall scores ranges from 0.0 (normal) to 10.0 (death due to MS). A sustained progression on EDSS score was defined as an EDSS progression confirmed into two consecutive assessment. Probability of disability progression at different time points was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first EDSS increase.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Number
95% Confidence Interval
Probability of Disability Progression
OLMP: Day 1, 90, 180, 270, 360, 450, 540, 630, 720 and 810
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Multiple Sclerosis (MS) According to the 2005 McDonald Criteria
The McDonald criteria use dissemination in time and space established by magnetic resonance imaging (MRI) findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new time constant 2 (T2) or gadolinium enhanced (Gd+) lesion found on a repeat MRI.
LTFU analysis set (No Treatment at LTFU Entry) consists of all participants who completed the 96-week ITP and entered the LTFU for safety follow-up and did not receive study treatment upon entry to the LTFU. Here "Number of Participants analyzed" signifies those participants who have been converted to CDMS.
Posted
Number
Days
Time from Randomization up to 1217 days
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number of Participants Analyzed" signifies those participants who have been converted to CDMS.
Posted
Number
Days
Time from Randomization up to 1217 days
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) According to Poser Criteria
CDMS according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months.
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number of Participants analyzed" signifies those participants who have been converted to CDMS.
Posted
Number
Days
Time from Randomization up to 1217 days
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Percentage of Participants Converting to Clinically Definite Multiple Sclerosis (CDMS) as Per Poser Criteria
Clinically definite multiple sclerosis (CDMS) according to the Poser criteria is defined as the occurrence of a second attack or a sustained increase in the expanded disability status scale (EDSS) Score. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. Sustained EDSS progression was defined as an increase in the EDSS score of greater than or equal to (>=) 1 point if baseline EDSS was between >= 1.0 and less than or equal to (=<) 4.5; or >= 1.5 points if baseline EDSS was 0, or >= 0.5 if baseline EDSS >= 5.0 over a period of at least 3 months. The percentage of participants who converted to CDMS are reported here.
ITT analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Percentage of participants
ITP: Baseline up to week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Secondary
ITP: Percentage of Participants Converting to McDonald Multiple Sclerosis (MS) (2005)
Percentage of participants converting to mcDonald multiple sclerosis (2005) were reported.
Intent-to-Treat analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Percentage of participants
ITP: Baseline up to week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Secondary
ITP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.
Posted
Mean
Standard Deviation
Lesions
OLMP: Baseline, Week 24, 48, 72 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Persisting Gd-enhanced Lesions
Number of new or persisting Gd-Enhanced lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
LTFU: Baseline, Week 13, 24, 36 and 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
The intent-to-treat (ITT) population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.
Posted
Mean
Standard Deviation
Lesions
OLMP: Baseline, Week 24, 48, 72 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of New or Enlarging T2 Lesions
Number of new or enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
LTFU: Baseline, Week 13, 24, 36 and 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
ITT population included all randomized participants who received at least 1 dose of ITP study medication. Here "Number of participants analyzed" signifies those who were evaluable for this outcome measure and "Number analyzed" signifies those participants who were evaluable at specified time point.
Posted
Mean
Standard Deviation
Lesions
ITP: Week 13, 24, 36, 48, 60, 72, 84 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Secondary
OLMP: Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of combined unique active (CUA) lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set included all participants who received at least 1 dose of study drug, converted to CDMS in ITP period, entered OLMP and received at least 1 dose of OLMP study drug. Here "Number of participants analyzed" = participants who were evaluable for this outcome measure and "Number analyzed" = who were evaluable at specified time point.
Posted
Mean
Standard Deviation
Lesions
OLMP: Baseline, Week 24, 48, 72 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA MRI lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Combined Unique Active (CUA) Magnetic Resonance Imaging (MRI) Lesions
Number of CUA lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
LTFU: Baseline, Week 13, 24, 36 and 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Change From Baseline in Volume of T1 Gd-Enhanced Lesions
Change in volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.
Posted
Mean
Standard Deviation
cubic millimeters (mm^3)
ITP: Baseline, Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Secondary
OLMP: Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.
Posted
Mean
Standard Deviation
mm^3
OLMP: Baseline, Week 24, 48, 72 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T1 Gd-Enhanced Lesions and Changes From Baseline in Volume of T1 Gd-Enhanced Lesions
Volume of T1 Gd-Enhanced lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Posted
Mean
Standard Deviation
mm^3
LTFU: Baseline, Week 13, 24, 36 and 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Changes From Baseline in Volume of T2 Lesions
Change in volume of T2 lesions from baseline was measured by using magnetic resonance imaging (MRI) scans.
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Posted
Mean
Standard Deviation
mm^3
ITP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set was used. Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Posted
Mean
Standard Deviation
mm^3
OLMP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Mean Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) was used.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Mean Volume of T2 Lesions and Changes From Baseline in Volume of T2 Lesions
Volume of T2 lesions was measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" = participants evaluable at specified timepoint.
Posted
Mean
Standard Deviation
mm^3
Baseline, Week 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
ITP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number analyzed" = participants evaluable at specified timepoint for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
OLMP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (Treated at LTFU Entry) analysis set consisted of all participants who converted to McDonald MS (2005) during the ITP, completed ITP 96-weeks and entered the LTFU.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of T1 Hypointense Lesions
Number of T1 Hypointense lesions were measured by using magnetic resonance imaging (MRI) scans.
LTFU analysis set (No Treatment at LTFU Entry) was used. Here "Number analyzed" signifies those participants who were evaluable at specified time point for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
LTFU: Baseline, Week 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Percentage of Participants
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
Posted
Number
Percentage of participants
OLMP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
LTFU analysis set (Treated at LTFU Entry) was used.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Persisting T1 Gd-Enhanced Lesions
T1 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or persisting T1 Gd-enhanced lesions were reported.
LTFU analysis set (No Treatment at LTFU Entry) was used.
Posted
Number
Percentage of participants
Baseline up to Week 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 lesions were reported.
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo).
Posted
Number
Percentage of Participants
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Secondary
OLMP: Percentage of Participants With no New or Enlarging T2 Lesions
T2 Gd-enhanced lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no new or enlarging T2 Lesions were reported.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
Posted
Number
Percentage of participants
OLMP: Baseline up to 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 Lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 Lesions were reported.
LTFU analysis set (Treated at LTFU Entry) was used.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Percentage of Participants With no New or Enlarging T2 Lesions
Enlarging T2 lesions were measured by using magnetic resonance imaging (MRI) scans. Percentage of participants with no New or Enlarging T2 lesions were reported.
LTFU analysis set (No Treatment at LTFU Entry) was used.
Posted
Number
Percentage of participants
LTFU: Baseline up to Week 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
ITP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
The ITT population included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.
Posted
Mean
Standard Deviation
Percent change
ITP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Secondary
OLMP: Percent Change From Baseline in Brain Volume
Brain volume was measured by using magnetic resonance imaging (MRI) scans. Percent change from baseline in brain volume at Week 48 and 96 was reported.
OLMP Analysis Set was used. Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure and "Number analyzed" = participants evaluable at specified timepoint.
Posted
Mean
Standard Deviation
Percent change
OLMP: Baseline, Week 48 and 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG001
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Secondary
OLMP: Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
Posted
Mean
Standard Deviation
Relapses
Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Secondary
LTFU (LTFU Analysis Set [Treated at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
LTFU analysis set (Treated at LTFU Entry) was used.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
LTFU (LTFU Analysis Set [No Treatment at LTFU Entry]): Number of Relapses
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
LTFU analysis set (No Treatment at LTFU Entry) was used.
Posted
Mean
Standard Deviation
Relapses
Baseline up to Week 48
ID
Title
Description
OG000
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Secondary
OLMP: Annualized Relapse Rate
The annualized relapse rate for each treatment group was the mean of the annualized relapse rates for all the participants in the group, calculated as the total number of confirmed relapses divided by the total number of days on study multiplied by 365.25. Where, Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif).
Posted
Number
95% Confidence Interval
relapses per year
Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Secondary
OLMP: Percentage of Relapse-Free Participants
Relapse was defined as new, worsening or recurrent neurological symptoms attributed to multiple sclerosis that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of relapse-free participants were reported.
OLMP Analysis Set included all participants who received at least 1 dose of study medication, converted to CDMS in the ITP period, entered the OLMP and received at least 1 dose of OLMP study drug (Rebif). Here "Number of participants analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Number
Percentage of participants
Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Secondary
ITP: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in the form of signs, symptoms, abnormal laboratory findings, or diseases that emerges or worsens relative to baseline during a clinical study with an Investigational Medicinal Product (IMP), regardless of causal relationship and even if no IMP has been administered. SAE: Any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was a medically important condition. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. Number of Participants with TEAEs and serious TEAEs were reported.
Safety analysis set included all randomized participants who received at least 1 dose of ITP study medication (cladribine or placebo) and had at least one safety assessment during the ITP.
Posted
Count of Participants
Participants
ITP: Baseline up to Week 96
ID
Title
Description
OG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
OG001
Cladribine 3.5 mg/kg (ITP)
Time Frame
ITP: Baseline up to 96 weeks; OLMP: Baseline up to 96 weeks; LTFU: Baseline up to 48 weeks
Description
ITP Safety analysis set(SAF). OLMP SAF: participants who received atleast 1dose of ITP study drug, converted to CDMS in ITP, entered OLMP and received atleast 1dose of OLMP study drug. LTFU (Treated)SAF: Participants who converted to McDonald MS(2005)during ITP, completed ITP 96-weeks and entered LTFU and treated with cladribine when entering LTFU. LTFU(Not-Treated) SAF:Participants who completed ITP 96-weeks and entered LTFU for safety follow-up and didn't receive study drug upon entry to LTFU.
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cladribine 5.25 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 milligrams per kilograms (mg/kg) over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48, and 52 resulting in total cladribine dose of 5.25 mg/kg during the ITP of 96 weeks or until clinically definite multiple sclerosis (CDMS) conversion, whichever occurred first.
0
204
12
204
133
204
EG001
Cladribine 3.5 mg/kg (ITP)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
0
206
23
206
132
206
EG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
0
206
22
206
116
206
EG003
Cladribine 5.25 mg/kg, Rebif (OLMP)
Participants who received cladribine 5.25 mg/kg and converted to CDMS during ITP entered in open-label maintenance period (OLMP) and received Rebif® new formulation (RNF) subcutaneously at a dose of 44 microgram (mcg) three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
0
24
1
24
18
24
EG004
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
1
25
4
25
19
25
EG005
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
0
9
0
9
4
9
EG008
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period . Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
0
16
1
16
7
16
EG009
Cladribine 5.25 mg/kg, Rebif (LTFU)
Participants who received cladribine 5.25 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
0
34
0
34
2
34
EG010
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
0
36
1
36
0
36
EG011
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
0
14
0
14
2
14
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Blood creatine phosphokinase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0003 affected204 at risk
EG0017 affected206 at risk
EG0024 affected206 at risk
EG0031 affected24 at risk
EG004
Blood uric acid increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Cardio-respiratory arrest
Cardiac disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hyperprolactinaemia
Endocrine disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Gastric ulcer perforation
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Injection site necrosis
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Erysipelas
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Pituitary tumour benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Calculus ureteric
Renal and urinary disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Nasal cyst
Respiratory, thoracic and mediastinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Psoriasis
Skin and subcutaneous tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0021 affected206 at risk
EG003
Blood amylase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0012 affected206 at risk
EG0020 affected206 at risk
EG003
Lipase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0012 affected206 at risk
EG0020 affected206 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Blood potassium increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Platelet count decreased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Thyroid neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0023 affected206 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0022 affected206 at risk
EG003
Papillary thyroid cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Skin papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Squamous cell carcinoma of skin
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Tonsillar neoplasm benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0022 affected206 at risk
EG003
Accidental overdose
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Back injury
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Clavicle fracture
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Gun shot wound
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Injury
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Joint sprain
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Ligament rupture
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Skin injury
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Thoracic vertebral fracture
Injury, poisoning and procedural complications
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Ovarian cyst
Reproductive system and breast disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0011 affected206 at risk
EG0021 affected206 at risk
EG003
Bartholin's cyst
Reproductive system and breast disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Fibrocystic breast disease
Reproductive system and breast disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Anogenital warts
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Herpes zoster
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Pilonidal cyst
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Arthropathy
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Neck pain
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Autoimmune thyroiditis
Endocrine disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hyperthyroidism
Endocrine disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Pulmonary oedema
Respiratory, thoracic and mediastinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Tracheal mass
Respiratory, thoracic and mediastinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Lymphopenia
Blood and lymphatic system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Atrial fibrillation
Cardiac disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Myocarditis
Cardiac disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Retinal vein thrombosis
Eye disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Mechanical ileus
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Cerebral haemorrhage
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Abortion spontaneous
Pregnancy, puerperium and perinatal conditions
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Delirium
Psychiatric disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Calculus urinary
Renal and urinary disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0020 affected206 at risk
EG003
Hypertension
Vascular disorders
MedDRA (11.0)
Non-systematic Assessment
EG0001 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Melanocytic naevus
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDRA (11.0)
Non-systematic Assessment
EG0002 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Lymphopenia
Blood and lymphatic system disorders
MedDRA (11.0)
Non-systematic Assessment
EG00047 affected204 at risk
EG00125 affected206 at risk
EG0020 affected206 at risk
EG0032 affected24 at risk
EG0041 affected25 at risk
EG0052 affected60 at risk
EG0060 affected9 at risk
EG0071 affected9 at risk
EG0080 affected16 at risk
EG0090 affected34 at risk
EG0100 affected36 at risk
EG0110 affected14 at risk
Nausea
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG00023 affected204 at risk
EG00124 affected206 at risk
EG00219 affected206 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG00011 affected204 at risk
EG00116 affected206 at risk
EG00213 affected206 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG00010 affected204 at risk
EG00115 affected206 at risk
EG0024 affected206 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0007 affected204 at risk
EG0019 affected206 at risk
EG00212 affected206 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0006 affected204 at risk
EG00114 affected206 at risk
EG0028 affected206 at risk
EG003
Fatigue
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG00015 affected204 at risk
EG00115 affected206 at risk
EG00219 affected206 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG00036 affected204 at risk
EG00135 affected206 at risk
EG00238 affected206 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG00023 affected204 at risk
EG00121 affected206 at risk
EG00217 affected206 at risk
EG003
Influenza
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG00014 affected204 at risk
EG00121 affected206 at risk
EG00213 affected206 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG00012 affected204 at risk
EG00110 affected206 at risk
EG00212 affected206 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG00014 affected204 at risk
EG00117 affected206 at risk
EG00213 affected206 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG00010 affected204 at risk
EG00113 affected206 at risk
EG00213 affected206 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG00010 affected204 at risk
EG00111 affected206 at risk
EG0029 affected206 at risk
EG003
Headache
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG00058 affected204 at risk
EG00164 affected206 at risk
EG00257 affected206 at risk
EG003
Dizziness
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG00012 affected204 at risk
EG00116 affected206 at risk
EG00219 affected206 at risk
EG003
Paraesthesia
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0009 affected204 at risk
EG00111 affected206 at risk
EG00210 affected206 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA (11.0)
Non-systematic Assessment
EG0005 affected204 at risk
EG0019 affected206 at risk
EG00212 affected206 at risk
EG003
Pharyngolaryngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG00016 affected204 at risk
EG00110 affected206 at risk
EG00210 affected206 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG00010 affected204 at risk
EG0018 affected206 at risk
EG00211 affected206 at risk
EG003
Leukopenia
Blood and lymphatic system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Eye pain
Eye disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Dental caries
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Influenza like illness
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Pyrexia
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Injection site reaction
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Injection site pain
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Injection site erythema
General disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0011 affected206 at risk
EG0021 affected206 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0021 affected206 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Musculoskeletal pain
Musculoskeletal and connective tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Food poisoning
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Gastrointestinal toxicity
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Radicular cyst
Gastrointestinal disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Drug hypersensitivity
Immune system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hypersensitivity
Immune system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Vaginal candidiasis
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Acute tonsillitis
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Bronchitis
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hordeolum
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Respiratory tract infection viral
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Wound
Infections and infestations
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Nystagmus
Nervous system disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Neurosis
Psychiatric disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Bartholin's cyst
Reproductive system and breast disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Hyperhidrosis
Skin and subcutaneous tissue disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Dysmenorrhoea
Reproductive system and breast disorders
MedDRA (11.0)
Non-systematic Assessment
EG0000 affected204 at risk
EG0010 affected206 at risk
EG0020 affected206 at risk
EG003
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Restriction Type
OTHER
Results Disclosure Restriction on PI(s)?
Yes
Other Details
Not provided
Point of Contact
Title
Organization
Phone
Extension
Email
Communication Center
Merck KGaA, Darmstadt, Germany
+49-6151-72-5200
service@emdgroup.com
ID
Term
D009103
Multiple Sclerosis
Ancestor Terms
ID
Term
D020278
Demyelinating Autoimmune Diseases, CNS
D020274
Autoimmune Diseases of the Nervous System
D009422
Nervous System Diseases
D003711
Demyelinating Diseases
D001327
Autoimmune Diseases
D007154
Immune System Diseases
Browse Leaves
Not provided
Browse Branches
Not provided
ID
Term
D017338
Cladribine
Ancestor Terms
ID
Term
D015762
2-Chloroadenosine
D000241
Adenosine
D011684
Purine Nucleosides
D011687
Purines
D006574
Heterocyclic Compounds, 2-Ring
D000072471
Heterocyclic Compounds, Fused-Ring
D006571
Heterocyclic Compounds
D003839
Deoxyadenosines
D003853
Deoxyribonucleosides
D009705
Nucleosides
D009706
Nucleic Acids, Nucleotides, and Nucleosides
D012263
Ribonucleosides
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
2 subjects
FG0057 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
23 subjects
FG00553 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
2 subjects
FG0042 subjects
FG0055 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Death
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0041 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Disease progression
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0054 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00315 subjects
FG00420 subjects
FG00544 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0069 subjects
FG0079 subjects
FG00817 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Lost to Follow-up
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0081 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0069 subjects
FG0078 subjects
FG00816 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
0 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG00934 subjects
FG01036 subjects
FG01114 subjects
0 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG00934 subjects
FG01036 subjects
FG01114 subjects
31.9
± 8.7
113
BG003334
Less than 30 years
BG00093
BG00196
BG00293
BG003282
138
BG003400
Male
BG00072
BG00176
BG00268
BG003216
1.6
± 0.9
BG0021.7± 0.9
BG0031.6± 0.9
0.9
± 2.5
BG0031.4± 4.5
26.3
± 27.4
BG00327.6± 28.4
79.40
± 17.94
BG00379.14± 17.17
112
BG002101
BG003321
Multifocal
Title
Measurements
BG00096
BG00194
BG002105
BG003295
140
BG003404
73
BG003237
< 0.0001
The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
Hazard Ratio (HR)
0.327
2-Sided
95
0.210
0.509
Superiority or Other (legacy)
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00051.36
OG00156.05
OG00287.14
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG002
two-sided Wald test
< 0.0001
The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
Hazard Ratio (HR)
0.425
2-Sided
95
0.331
0.547
Superiority or Other (legacy)
OG001
OG002
two-sided Wald test
< 0.0001
The treatment effect was also assessed by hazard ratios using the Cox's proportional hazards model.
Hazard Ratio (HR)
0.497
2-Sided
95
0.390
0.633
Superiority or Other (legacy)
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000203
OG001202
OG002196
Title
Denominators
Categories
CUA lesions
Title
Measurements
OG0001.20± 5.79
OG0010.65± 1.80
OG0022.13± 2.87
New or persisting T1 Gd+ lesions
Title
Measurements
OG0000.61± 5.33
OG0010.29± 0.97
OG0020.97± 1.62
New or enlarging T2 lesions
Title
Measurements
OG0000.62± 1.90
OG0010.40± 1.12
OG0021.17± 1.87
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG001
OG002
CUA lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.667
2-Sided
95
-0.971
-0.500
Superiority
OG000
OG002
CUA lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.625
2-Sided
95
-0.857
-0.429
Superiority
OG001
OG002
T1 Gd-Enhancing Lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.286
2-Sided
95
-0.333
-0.167
Superiority
OG000
OG002
T1 Gd-Enhancing Lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.286
2-Sided
95
-0.375
-0.167
Superiority
OG001
OG002
T2 Lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.333
2-Sided
95
-0.500
-0.167
Superiority
OG000
OG002
T2 Lesions
ANCOVA
<0.0001
Median Difference (Final Values)
-0.286
2-Sided
95
-0.429
-0.143
Superiority
Cladribine 3.5 mg/kg, Rebif (OLMP)
Participants who received cladribine 3.5 mg/kg and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
OG002
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Day 1
ParticipantsOG00024
ParticipantsOG00125
ParticipantsOG00260
Title
Measurements
OG0000.0000(0.0000 to 0.0000)
OG0010.0000(0.0000 to 0.0000)
OG0020.0000(0.0000 to 0.0000)
Day 90
ParticipantsOG00024
ParticipantsOG00124
ParticipantsOG00259
Title
Measurements
OG000
Day 180
ParticipantsOG00022
ParticipantsOG00121
ParticipantsOG00252
Title
Measurements
OG000
Day 270
ParticipantsOG00021
ParticipantsOG00118
ParticipantsOG00247
Title
Measurements
OG000
Day 360
ParticipantsOG00018
ParticipantsOG00114
ParticipantsOG00240
Title
Measurements
OG000
Day 450
ParticipantsOG00012
ParticipantsOG00110
ParticipantsOG00230
Title
Measurements
OG000
Day 540
ParticipantsOG00011
ParticipantsOG0015
ParticipantsOG00222
Title
Measurements
OG000
Day 630
ParticipantsOG0007
ParticipantsOG0013
ParticipantsOG00213
Title
Measurements
OG000
Day 720
ParticipantsOG0003
ParticipantsOG0012
ParticipantsOG0022
Title
Measurements
OG000
Day 810
ParticipantsOG0000
ParticipantsOG0010
ParticipantsOG0020
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0001
OG0010
OG0020
Title
Denominators
Categories
Title
Measurements
OG000773
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0001
OG0010
OG0020
Title
Denominators
Categories
Title
Measurements
OG000773
OG001
Cladribine 3.5 mg/kg, Rebif (LTFU)
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who converted to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0000
OG0010
OG0021
Title
Denominators
Categories
Title
Measurements
OG002767
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00028.8
OG00123.1
OG00256.3
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00070.7
OG00171.6
OG00291.8
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Week 13
ParticipantsOG000188
ParticipantsOG001189
ParticipantsOG002192
Title
Measurements
OG0000.86± 5.60
OG0010.37± 1.52
OG0021.00± 1.98
Week 24
ParticipantsOG000171
ParticipantsOG001186
ParticipantsOG002166
Title
Measurements
OG000
Week 36
ParticipantsOG000105
ParticipantsOG001115
ParticipantsOG002100
Title
Measurements
OG000
Week 48
ParticipantsOG000163
ParticipantsOG001173
ParticipantsOG002143
Title
Measurements
OG000
Week 60
ParticipantsOG000145
ParticipantsOG001148
ParticipantsOG002131
Title
Measurements
OG000
Week 72
ParticipantsOG000128
ParticipantsOG001146
ParticipantsOG002115
Title
Measurements
OG000
Week 84
ParticipantsOG000116
ParticipantsOG001126
ParticipantsOG00283
Title
Measurements
OG000
Week 96
ParticipantsOG00070
ParticipantsOG00180
ParticipantsOG00249
Title
Measurements
OG000
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00124
OG00259
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00124
ParticipantsOG00259
Title
Measurements
OG0001.38± 5.52
OG0010.88± 1.80
OG0021.27± 2.58
Week 24
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00257
Title
Measurements
OG000
Week 48
ParticipantsOG00019
ParticipantsOG00115
ParticipantsOG00246
Title
Measurements
OG000
Week 72
ParticipantsOG00011
ParticipantsOG0018
ParticipantsOG00230
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Baseline
ParticipantsOG0009
ParticipantsOG0019
ParticipantsOG00217
Title
Measurements
OG0000.00± 0.00
OG0010.00± 0.00
OG0020.71± 1.16
Week 13
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00216
Title
Measurements
OG000
Week 24
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00211
Title
Measurements
OG000
Week 36
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG00210
Title
Measurements
OG000
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0000.00± 0.00
OG0010.06± 0.23
OG0020.14± 0.36
Week 13
ParticipantsOG00022
ParticipantsOG00123
ParticipantsOG00211
Title
Measurements
OG000
Week 24
ParticipantsOG00015
ParticipantsOG00115
ParticipantsOG0025
Title
Measurements
OG000
Week 36
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0023
Title
Measurements
OG000
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Week 13
ParticipantsOG000188
ParticipantsOG001189
ParticipantsOG002192
Title
Measurements
OG0001.56± 3.52
OG0011.25± 3.33
OG0021.43± 2.56
Week 24
ParticipantsOG000171
ParticipantsOG001186
ParticipantsOG002166
Title
Measurements
OG000
Week 36
ParticipantsOG000104
ParticipantsOG001115
ParticipantsOG002100
Title
Measurements
OG000
Week 48
ParticipantsOG000165
ParticipantsOG001174
ParticipantsOG002143
Title
Measurements
OG000
Week 60
ParticipantsOG000145
ParticipantsOG001148
ParticipantsOG002131
Title
Measurements
OG000
Week 72
ParticipantsOG000128
ParticipantsOG001148
ParticipantsOG002116
Title
Measurements
OG000
Week 84
ParticipantsOG000116
ParticipantsOG001127
ParticipantsOG00283
Title
Measurements
OG000
Week 96
ParticipantsOG00069
ParticipantsOG00179
ParticipantsOG00250
Title
Measurements
OG000
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00124
OG00260
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00124
ParticipantsOG00260
Title
Measurements
OG0000.29± 0.75
OG0011.54± 6.72
OG0022.13± 7.29
Week 24
ParticipantsOG00023
ParticipantsOG00122
ParticipantsOG00257
Title
Measurements
OG000
Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00246
Title
Measurements
OG000
Week 72
ParticipantsOG00011
ParticipantsOG0018
ParticipantsOG00230
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Baseline
ParticipantsOG0009
ParticipantsOG0019
ParticipantsOG00217
Title
Measurements
OG0000.00± 0.00
OG0010.00± 0.00
OG0020.71± 1.53
Week 13
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00216
Title
Measurements
OG000
Week 24
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00211
Title
Measurements
OG000
Week 36
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG00210
Title
Measurements
OG000
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0000.00± 0.00
OG0010.03± 0.17
OG0020.07± 0.27
Week 13
ParticipantsOG00021
ParticipantsOG00123
ParticipantsOG00211
Title
Measurements
OG000
Week 24
ParticipantsOG00015
ParticipantsOG00115
ParticipantsOG0025
Title
Measurements
OG000
Week 36
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0023
Title
Measurements
OG000
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000189
OG001189
OG002192
Title
Denominators
Categories
Week 13
ParticipantsOG000189
ParticipantsOG001189
ParticipantsOG002192
Title
Measurements
OG0002.37± 6.87
OG0011.56± 4.04
OG0022.41± 3.89
Week 24
ParticipantsOG000171
ParticipantsOG001186
ParticipantsOG002166
Title
Measurements
OG000
Week 36
ParticipantsOG000105
ParticipantsOG001115
ParticipantsOG002100
Title
Measurements
OG000
Week 48
ParticipantsOG000165
ParticipantsOG001174
ParticipantsOG002143
Title
Measurements
OG000
Week 60
ParticipantsOG000145
ParticipantsOG001149
ParticipantsOG002131
Title
Measurements
OG000
Week 72
ParticipantsOG000128
ParticipantsOG001148
ParticipantsOG002116
Title
Measurements
OG000
Week 84
ParticipantsOG000116
ParticipantsOG001128
ParticipantsOG00283
Title
Measurements
OG000
Week 96
ParticipantsOG00070
ParticipantsOG00180
ParticipantsOG00250
Title
Measurements
OG000
Placebo, Rebif (OLMP)
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00124
OG00260
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00124
ParticipantsOG00260
Title
Measurements
OG0000.63± 1.17
OG0012.17± 7.72
OG0023.23± 8.07
Week 24
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00257
Title
Measurements
OG000
Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00246
Title
Measurements
OG000
Week 72
ParticipantsOG00011
ParticipantsOG0018
ParticipantsOG00230
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
Participants who received cladribine 3.5 mg/kg and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Baseline
ParticipantsOG0009
ParticipantsOG0019
ParticipantsOG00217
Title
Measurements
OG0000.00± 0.00
OG0010.00± 0.00
OG0021.24± 2.49
Week 13
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00216
Title
Measurements
OG000
Week 24
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00211
Title
Measurements
OG000
Week 36
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG00210
Title
Measurements
OG000
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0000.00± 0.00
OG0010.03± 0.17
OG0020.14± 0.36
Week 13
ParticipantsOG00022
ParticipantsOG00123
ParticipantsOG00211
Title
Measurements
OG000
Week 24
ParticipantsOG00015
ParticipantsOG00115
ParticipantsOG0025
Title
Measurements
OG000
Week 36
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0023
Title
Measurements
OG000
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000203
OG001203
OG002197
Title
Denominators
Categories
Title
Measurements
OG000-73.97± 204.80
OG001-126.64± 399.39
OG00248.63± 239.03
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG001
OG002
ANCOVA
<0.0001
Point Estimate
-1.700
2-Sided
95
-37.200
0.000
Superiority
OG000
OG002
ANCOVA
<0.0001
Point Estimate
-28.600
2-Sided
95
-117.300
0.000
Superiority
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00124
OG00260
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00124
ParticipantsOG00260
Title
Measurements
OG00091.06± 368.98
OG001113.64± 248.74
OG002136.61± 344.31
Week 24
ParticipantsOG00023
ParticipantsOG00123
ParticipantsOG00257
Title
Measurements
OG000
Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00246
Title
Measurements
OG000
Week 72
ParticipantsOG00011
ParticipantsOG0018
ParticipantsOG00231
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
Change at Week 24
ParticipantsOG00023
ParticipantsOG00123
ParticipantsOG00257
Title
Measurements
OG000
Change at Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00246
Title
Measurements
OG000
Change at Week 72
ParticipantsOG00011
ParticipantsOG0018
ParticipantsOG00231
Title
Measurements
OG000
Change at Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Baseline
ParticipantsOG0009
ParticipantsOG0019
ParticipantsOG00217
Title
Measurements
OG0000.00± 0.00
OG0010.00± 0.00
OG00279.43± 143.64
Week 13
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00216
Title
Measurements
OG000
Week 24
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00211
Title
Measurements
OG000
Week 36
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG00210
Title
Measurements
OG000
Change at Week 13
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00216
Title
Measurements
OG000
Change at Week 24
ParticipantsOG0007
ParticipantsOG0018
ParticipantsOG00211
Title
Measurements
OG000
Change at Week 36
ParticipantsOG0002
ParticipantsOG0013
ParticipantsOG00210
Title
Measurements
OG000
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0000.00± 0.00
OG0014.45± 21.25
OG00227.79± 76.02
Week 13
ParticipantsOG00022
ParticipantsOG00123
ParticipantsOG00211
Title
Measurements
OG000
Week 24
ParticipantsOG00015
ParticipantsOG00115
ParticipantsOG0025
Title
Measurements
OG000
Week 36
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0023
Title
Measurements
OG000
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Change at Week 13
ParticipantsOG00022
ParticipantsOG00123
ParticipantsOG00211
Title
Measurements
OG000
Change at Week 24
ParticipantsOG00015
ParticipantsOG00115
ParticipantsOG0025
Title
Measurements
OG000
Change at Week 36
ParticipantsOG0004
ParticipantsOG0017
ParticipantsOG0023
Title
Measurements
OG000
Change at Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Baseline
ParticipantsOG000204
ParticipantsOG001206
ParticipantsOG002206
Title
Measurements
OG0003825.73± 5093.52
OG0013435.22± 5184.12
OG0023436.69± 4613.43
Change at Week 48
ParticipantsOG000165
ParticipantsOG001174
ParticipantsOG002143
Title
Measurements
OG000
Change at Week 96
ParticipantsOG00070
ParticipantsOG00181
ParticipantsOG00251
Title
Measurements
OG000
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00125
ParticipantsOG00260
Title
Measurements
OG000398.88± 1102.27
OG001630.70± 1707.24
OG0021019.30± 2872.03
Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00247
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
Change at Week 48
ParticipantsOG00019
ParticipantsOG00116
ParticipantsOG00247
Title
Measurements
OG000
Change at Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Title
Measurements
OG0001217.53± 1991.21
OG001587.79± 1491.20
OG002702.30± 1254.66
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0001402.08± 1799.96
OG001962.26± 1026.99
OG0021407.75± 1890.94
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Change at Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Baseline
ParticipantsOG000204
ParticipantsOG001206
ParticipantsOG002206
Title
Measurements
OG0008.0± 11.7
OG0017.3± 12.2
OG0027.0± 8.6
Week 48
ParticipantsOG000162
ParticipantsOG001171
ParticipantsOG002141
Title
Measurements
OG000
Week 96
ParticipantsOG00069
ParticipantsOG00179
ParticipantsOG00248
Title
Measurements
OG000
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Baseline
ParticipantsOG00024
ParticipantsOG00125
ParticipantsOG00260
Title
Measurements
OG0000.92± 2.22
OG0012.32± 9.52
OG0021.45± 3.53
Week 48
ParticipantsOG00019
ParticipantsOG00115
ParticipantsOG00246
Title
Measurements
OG000
Week 96
ParticipantsOG0006
ParticipantsOG0013
ParticipantsOG00215
Title
Measurements
OG000
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Title
Measurements
OG0004.44± 7.25
OG0011.22± 3.31
OG0022.24± 5.01
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Baseline
ParticipantsOG00034
ParticipantsOG00136
ParticipantsOG00214
Title
Measurements
OG0005.74± 8.21
OG0013.53± 5.78
OG0022.93± 4.46
Week 48
ParticipantsOG0001
ParticipantsOG0010
ParticipantsOG0020
Title
Measurements
OG000
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00067.0
OG00157.1
OG00221.6
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Title
Measurements
OG00025.0
OG00150.0
OG00235.3
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000204
OG001206
OG002206
Title
Denominators
Categories
Title
Measurements
OG00032.9
OG00135.1
OG00219.0
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Title
Measurements
OG00018.2
OG00116.7
OG00213.5
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG000155
OG001163
OG002135
Title
Denominators
Categories
Week 48
ParticipantsOG000155
ParticipantsOG001163
ParticipantsOG002135
Title
Measurements
OG000-0.47± 0.63
OG001-0.48± 0.69
OG002-0.33± 0.76
Week 96
ParticipantsOG00053
ParticipantsOG00151
ParticipantsOG00232
Title
Measurements
OG000
Participants who received placebo and converted to CDMS during ITP entered in OLMP and received RNF subcutaneously at a dose of 44 mcg three times a week for up to 96 weeks. Due to trial termination, the OLMP duration was reduced for some participants.
Units
Counts
Participants
OG0005
OG0014
OG00211
Title
Denominators
Categories
Week 48
ParticipantsOG0005
ParticipantsOG0014
ParticipantsOG00211
Title
Measurements
OG000-0.41± 0.98
OG001-1.60± 1.40
OG002-0.56± 1.11
Week 96
ParticipantsOG0003
ParticipantsOG0010
ParticipantsOG0023
Title
Measurements
OG000
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Title
Measurements
OG0000.33± 0.64
OG0010.16± 0.37
OG0020.55± 1.00
OG002
Placebo, Rebif, Cladribine 3.5 mg/kg (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in long-term follow-up (LTFU) period. Participants who converted to McDonald multiple sclerosis (MS) during ITP or during LTFU period received open-label cladribine tablets (3.5 mg/kg) during LTFU period. Participants who converted to CDMS during LTFU received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG0009
OG0019
OG00217
Title
Denominators
Categories
Title
Measurements
OG0000.00± 0.00
OG0010.00± 0.00
OG0020.06± 0.24
OG002
Placebo, Rebif (LTFU)
Participants who received placebo and did not convert to CDMS during ITP, entered in LTFU period. Participants who did not convert to McDonald MS during ITP did not receive any treatment during LTFU period. Participants who convert to CDMS during LTFU period received RNF subcutaneously at a dose of 44 mcg three times a week for the remaining LTFU period. Under the original study design, total duration of LTFU period was up to 96 weeks. The LTFU duration was reduced due to trial termination. Following the notice of trial termination, no further open label cladribine treatment was administered during the LTFU.
Units
Counts
Participants
OG00034
OG00136
OG00214
Title
Denominators
Categories
Title
Measurements
OG0000.03± 0.17
OG0010.03± 0.17
OG0020.00± 0.00
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG00024
OG00125
OG00260
Title
Denominators
Categories
Title
Measurements
OG0000.24(0.07 to 0.40)
OG0010.14(0.00 to 0.27)
OG0020.42(0.28 to 0.56)
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
Units
Counts
Participants
OG00010
OG0015
OG00226
Title
Denominators
Categories
Title
Measurements
OG00040.0
OG00120.0
OG00230.8
Cladribine tablets administered as cumulative dose of 0.875 mg/kg over a course of 5 consecutive days at Weeks 1, 5, 48, 52 and placebo matched to cladribine tablets was administered at Week 9 and 13 resulting in total cladribine dose of 3.5 mg/kg during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.
OG002
Placebo (ITP)
Placebo matched to cladribine tablets administered over a course of 5 consecutive days at Weeks 1, 5, 9, 13, 48 and 52 during the ITP of 96 weeks or until CDMS conversion, whichever occurred first.