Long-term Follow-Up of Patients Who Participated in Study... | NCT00813709 | Trialant
NCT00813709
Sponsor
Merck KGaA, Darmstadt, Germany
Status
Completed
Last Update Posted
Mar 8, 2017Actual
Enrollment
402Actual
Phase
Phase 3
Conditions
Multiple Sclerosis
Clinically Isolated Syndrome
Interventions
RNF
RNF
RNF
Placebo
Countries
Argentina
Austria
Belgium
Bulgaria
Canada
Croatia
Czechia
Estonia
Finland
France
Germany
Greece
Israel
Italy
Latvia
Lebanon
Morocco
Poland
Portugal
Romania
Russia
Serbia
Slovakia
Spain
Protocol Section
Identification Module
NCT ID
NCT00813709
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
28981
Secondary IDs
Not provided
Brief Title
Long-term Follow-Up of Patients Who Participated in Study 27025 (REFLEX)
Official Title
Double-blind Extension of the Study 27025 (REFLEX) to Obtain Long-term Follow-up Data in Patients With Clinically Definite MS and Patients With a First Demyelinating Event at High Risk of Converting to MS, Treated With Rebif® New Formulation (REFLEXION)
Acronym
REFLEXION
Organization
Merck KGaA, Darmstadt, GermanyINDUSTRY
Status Module
Record Verification Date
Jan 2017
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 2008
Primary Completion Date
Aug 2011Actual
Completion Date
Sep 2013Actual
First Submitted Date
Dec 22, 2008
First Submission Date that Met QC Criteria
Dec 22, 2008
First Posted Date
Dec 23, 2008Estimated
Results Waived
Not provided
Results First Submitted Date
Nov 27, 2012
Results First Submitted that Met QC Criteria
Oct 25, 2013
Results First Posted Date
Oct 28, 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
Jan 25, 2017
Last Update Posted Date
Mar 8, 2017Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
Merck KGaA, Darmstadt, GermanyINDUSTRY
Collaborators
Not provided
Oversight Module
No data available
No data is available for this block.
Description Module
Brief Summary
REFLEXION is a double blind extension of the study 27025 (NCT00404352) (REFLEX). The purpose of the study is to obtain long-term follow-up data in subjects with clinically definite multiple sclerosis (MS) and subjects with a first demyelinating event at high risk of converting to MS, treated with fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of interferon [IFN]-beta-1a (RNF).
Detailed Description
The objective of the study is to investigate whether RNF treatment initiated after the first clinical event versus delayed treatment results in the prolongation of time to Clinically Definite Multiple Sclerosis (CDMS) conversion up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX). Furthermore, the study is intended to explore whether RNF treatment initiated after the first clinical event versus delayed treatment delays disability (including development of secondary progressive MS) and reduces disease activity (including the annual relapse rate [ARR]) in the long term (up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX). The study will also assess the long-term safety profile of RNF (up to Month 36 and up to Month 60 since randomization in Study 27025 (REFLEX).
Conditions Module
Conditions
Multiple Sclerosis
Clinically Isolated Syndrome
Keywords
Interferon 1-beta
Clinical Definite 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
402Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
RNF 44 mcg thrice weekly
Active Comparator
Drug: RNF
RNF 44 mcg once weekly and placebo
Active Comparator
Drug: RNF
Drug: Placebo
Placebo/RNF 44 mcg thrice weekly
Active Comparator
Drug: RNF
Interventions
Name
Type
Description
Arm Group Labels
Other Names
RNF
Drug
Single dose of RNF will be administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months
CDMS was defined by the occurrence of a second attack or relapse over 36 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.
Baseline (Day 1 of Study 27025) up to 36 Months
Secondary Outcomes
Measure
Description
Time Frame
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. Time to confirmed EDSS progression was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with confirmed EDSS progression.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Reach scheduled end of study in Study 27025 (REFLEX) (completion of 24 months participation)
Medical assessment by the Investigator/treating physician from study 27025 that there is no objection to the subject's participation in this extension trial considering the medical experience from Study 27025 (REFLEX). Special attention should be given to laboratory abnormalities and clinically significant liver, renal and bone-marrow dysfunction
If female, subject must:
be neither pregnant nor breast-feeding, nor attempting to conceive
use a highly effective method of contraception. A highly effective method of contraception is defined as those which result in a low failure rate (that is [i.e.] less than 1 percent [%] per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence or vasectomized partner
Subject is willing to follow study procedures
Subject has given written informed consent
Exclusion Criteria:
Subject has any disease other than MS that could better explain the subject's signs and symptoms
Subject has a primary progressive course of MS
Subject has total bilirubin greater than 2.5 times upper limit of normal (ULN) at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
Subject has total aspartate aminotransferase (AST) or alanine aminotransferase (ALT) or alkaline phosphatase (ALP) greater than 2.5 times the ULN values at both Month 24 and at the previous visit (i.e. Month 21) (subjects with greater than 2.5 times ULN at Month 24 only are eligible for enrollment and should be managed as per label recommendations until normalization of the value)
Subject suffers from another current autoimmune disease
Subject suffers from major medical or psychiatric illness (including history of, or current, severe depressive disorders and/or suicidal ideation) that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol
Subject has a history of seizures not adequately controlled by treatment
Subject has cardiac disease, such as angina, congestive heart failure or arrhythmia
Subject has a known allergy to IFN-beta or the excipient(s) of the study medication
Subject has any condition that could interfere with the MRI evaluation
Subject has a known allergy to gadolinium-diethylene triamine pentaacetic acid (DTPA)
Subject has a history of alcohol or drug abuse
Subject has previously participated in this study
Subject has moderate to severe renal impairment
Subject is pregnant or lactating
Subject has any medical, psychiatric or other conditions that compromise his/her ability to understand the subject information, to give informed consent, to comply with the study protocol, or to complete the study
Comi G, De Stefano N, Freedman MS, Barkhof F, Uitdehaag BM, de Vos M, Marhardt K, Chen L, Issard D, Kappos L. Subcutaneous interferon beta-1a in the treatment of clinically isolated syndromes: 3-year and 5-year results of the phase III dosing frequency-blind multicentre REFLEXION study. J Neurol Neurosurg Psychiatry. 2017 Apr;88(4):285-294. doi: 10.1136/jnnp-2016-314843. Epub 2016 Dec 30.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Results Section
Participant Flow Module
Pre-assignment Details
517 participants randomized in Study 27025 used in this study as integrated intention to treat (ITT) population. Out of the 517, 402 participants took part in study 28981: 300 comprised the double blind (DB) population and 122 comprised the open label (OL) population (some participants (20) were included in both populations)
Recruitment Details
Participants who were randomized in Study 27025 (NCT00404352) were eligible to enroll into extension Study 28981 (NCT00813709) whether or not they completed main study on Investigational Medicinal Product (IMP), or no treatment or received other disease-modifying drugs (DMDs) during course of main study. No re-randomization was done for this study.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Placebo/RNF 44 Mcg Thrice Weekly (DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
Periods
Title
Milestones
Reasons Not Completed
Double Blind Period
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Saudi Arabia
Turkey (Türkiye)
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
Double
Masking Description
Not provided
Who Masked
ParticipantInvestigator
RNF 44 mcg thrice weekly
Rebif®
RNF
Drug
Single dose of RNF will be administered subcutaneously once weekly at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
RNF 44 mcg once weekly and placebo
Rebif®
RNF
Drug
Participants who were initially randomized in Study 27025 (REFLEX) to the placebo treatment group will be switched to single dose of RNF administered subcutaneously three times weekly at least 48 hours apart at a dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Placebo/RNF 44 mcg thrice weekly
Rebif®
Placebo
Drug
Single dose matching placebo will be administered subcutaneously twice weekly. Placebo is supplied as a transparent, sterile solution for injection in pre-filled syringes matching the RNF pre-filled syringes, each containing 0.5 milliliter (mL).
RNF 44 mcg once weekly and placebo
Baseline (Day 1 of Study 27025) up to 36 Months
Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Lesions Per Participant Per Scan at Month 36
Number of CUA lesions, new T2 lesions, new Gd+ lesions and new T1 lesions were measured by using MRI scans.
Month 36
Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36
Change from baseline in lesion volume was measured by using MRI scans for T1 hypointense lesions and T2 lesions at Month 36
Baseline (Day 1 of Study 27025), Month 36
Percent Change From Baseline in Brain Volume at Month 36
Percent change in brain volume was measured by using MRI scans.
Baseline (Day 1 of Study 27025), Month 36
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new T2 or 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.
Baseline (Day 1 of Study 27025) up to CDMS conversion and/or up to 36 Months
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36
The Paced Auditory Serial Addition Test (PASAT) is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Score ranges from '0-60'. Higher scores reflect better neurological function and a positive change from baseline indicates improvement.
Baseline (Day of Study 27025), Month 36
Percentage of Relapse-Free Participants at Month 36
A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Month 36
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS score at Month 36 was calculated as EDSS score at Month 36 minus EDSS score at baseline.
Baseline (Day of Study 27025), Month 36
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Baseline (Day 1 of Study 27025), Month 36
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36
BAbs are all antibodies which are capable of binding to the investigational drug molecule (RNF) irrespective of their binding site. NAbs are defined as a subgroup of BAbs which bind to the active sites of the RNF and therefore neutralize its potency. NAbs were detected using a viral cytopathic assay. BAbs were measured by using an ELISA (Enzyme-linked immunosorbent assay).
Month 36
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
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.
Month 24 up to Month 36 (DB treatment period for study 28981 (REFLEXION)
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to Month 60
CDMS was defined by the occurrence of a second attack or relapse over 60 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.
Baseline (Day 1 of Study 27025) up to 60 Months
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. Time to confirmed EDSS progression was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with confirmed EDSS progression.
Baseline (Day 1 of Study 27025) up to 60 Months
Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New T1 Lesions Per Participant Per Scan at Month 60
Number of CUA lesions, new T2 lesions, new Gd+ Lesions and new T1 lesions were measured by using MRI scans.
Month 60
Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60
Change from baseline in lesion volume was measured by using MRI scans for T1 hypointense lesions and T2 lesions.
Baseline (Day 1 of Study 27025), Month 60
Percent Change From Baseline in Brain Volume at Month 60
Percent Change in brain volume was measured by using MRI scans.
Baseline (Day 1 of Study 27025), Month 60
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new T2 or 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.
Month 60
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Score ranges from '0-60'. Higher scores reflect better neurological function and a positive change from baseline indicates improvement.
Baseline (Day 1 of Study 27025), Month 60
Percentage of Relapse-Free Participants at Month 60
A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Month 60
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS score at Month 60 was calculated as EDSS score at Month 60 minus EDSS score at baseline.
Baseline (Day 1 of Study 27025), Month 60
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Baseline (Day 1 of Study 27025), Month 60
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60
BAbs are all antibodies which are capable of binding to the RNF irrespective of their binding site. NAbs are defined as a subgroup of BAbs which bind to the active sites of the RNF and therefore neutralize its potency. NAbs were detected using a viral cytopathic assay. BAbs were measured by using an ELISA.
Month 60
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
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.
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
FG002
RNF 44 Mcg Thrice Weekly (DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
FG003
Placebo/RNF 44 Mcg Thrice Weekly/OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
FG004
RNF 44 Mcg Once Weekly /OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
FG005
RNF 44 Mcg Thrice Weekly/OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
FG00084 subjects
FG001117 subjects
FG00299 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Treated
FG00083 subjects
FG001114 subjects
FG00298 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
COMPLETED
FG00053 subjects
FG00176 subjects
FG00268 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
NOT COMPLETED
FG00031 subjects
FG00141 subjects
FG00231 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Type
Comment
Reasons
Adverse Event
FG0004 subjects
FG0011 subjects
FG0024 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
Lost to Follow-up
FG0003 subjects
FG0012 subjects
FG0022 subjects
FG0030 subjects
FG004
Switched to open label phase
FG0009 subjects
FG00126 subjects
FG00218 subjects
FG0030 subjects
FG004
Randomized but not treated
FG0001 subjects
FG0013 subjects
FG0021 subjects
FG0030 subjects
FG004
Other
FG00014 subjects
FG0019 subjects
FG0026 subjects
FG0030 subjects
FG004
Open Label Period
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00358 subjects49 participants in OL period initially + 9 participants from DB converted to CDMS during the study
FG00451 subjects25 participants in OL period initially + 26 participants from DB converted to CDMS during the study
FG00546 subjects28 participants in OL period initially + 18 participants from DB converted to CDMS during the study
Treated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00357 subjects
FG004
COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00338 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00320 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline data was presented for ITT population (402 participants) which included participants who had completed the REFLEX Study 27025 (NCT00404352) and were enrolled in this extension Study 28981 (REFLEXION).
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo/RNF 44 Mcg Thrice Weekly (ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of RNF injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months. 84 participants were initially assigned to DB RNF 44 mcg thrice weekly and 49 participants were initially assigned to OL RNF 44 mcg thrice weekly (9 participants from DB converted to CDMS and switched to OL period over course of this study)
BG001
RNF 44 Mcg Once Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 117 participants were initially assigned to DB RNF 44 mcg thrice weekly and 25 participants were initially assigned to OL RNF 44 mcg thrice weekly (26 participants from DB converted to CDMS and switched to OL period over course of this study)
BG002
RNF 44 Mcg Thrice Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 99 participants were initially assigned to DB RNF 44 mcg thrice weekly and 28 participants were initially assigned to OL RNF 44 mcg thrice weekly (18 participants from DB converted to CDMS and switched to OL period over course of this study)
BG003
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG000133
BG001142
BG002127
BG003402
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
BG00031.0± 8.2
BG00131.4± 8.2
BG00231.8± 8.6
BG003
Age, Customized
Number
participants
Title
Denominators
Categories
Less than 30 years
Title
Measurements
BG00067
BG00166
BG002
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00082
BG00188
BG002
Race/Ethnicity, Customized
Number
participants
Title
Denominators
Categories
Black
Title
Measurements
BG0000
BG0011
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
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to 36 Months
CDMS was defined by the occurrence of a second attack or relapse over 36 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
95% Confidence Interval
Cumulative % of participants with CDMS
Baseline (Day 1 of Study 27025) up to 36 Months
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00041.3(33.5 to 49.1)
OG00127.6(20.6 to 34.6)
OG00227.1(19.9 to 34.3)
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
Log Rank
0.002
Hazard Ratio (HR)
0.555
2-Sided
95
0.378
0.816
Superiority or Other
OG000
OG001
Log Rank
0.006
Secondary
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 36 Months
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. Time to confirmed EDSS progression was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with confirmed EDSS progression.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
% of participants with EDSS progression
Baseline (Day 1 of Study 27025) up to 36 Months
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Secondary
Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New Time Constant 1 (T1) Lesions Per Participant Per Scan at Month 36
Number of CUA lesions, new T2 lesions, new Gd+ lesions and new T1 lesions were measured by using MRI scans.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure at this time point.
Posted
Mean
Standard Deviation
lesions
Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG001
Secondary
Change From Baseline in Time Constant 1 (T1) Hypointense Lesion Volume and Time Constant 2 (T2) Lesion Volume at Month 36
Change from baseline in lesion volume was measured by using MRI scans for T1 hypointense lesions and T2 lesions at Month 36
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
cubic millimeter (mm^3)
Baseline (Day 1 of Study 27025), Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG001
Secondary
Percent Change From Baseline in Brain Volume at Month 36
Percent change in brain volume was measured by using MRI scans.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure at this time point.
Posted
Mean
Standard Deviation
percent change
Baseline (Day 1 of Study 27025), Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Secondary
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) up to 36 Months
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new T2 or 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.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
percentage of participants
Baseline (Day 1 of Study 27025) up to CDMS conversion and/or up to 36 Months
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Secondary
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 36
The Paced Auditory Serial Addition Test (PASAT) is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Score ranges from '0-60'. Higher scores reflect better neurological function and a positive change from baseline indicates improvement.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
units on a scale
Baseline (Day of Study 27025), Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Secondary
Percentage of Relapse-Free Participants at Month 36
A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
Percentage of participants
Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 36
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS score at Month 36 was calculated as EDSS score at Month 36 minus EDSS score at baseline.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
units on a scale
Baseline (Day of Study 27025), Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Secondary
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 36
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
Z-score
Baseline (Day 1 of Study 27025), Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Secondary
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 36
BAbs are all antibodies which are capable of binding to the investigational drug molecule (RNF) irrespective of their binding site. NAbs are defined as a subgroup of BAbs which bind to the active sites of the RNF and therefore neutralize its potency. NAbs were detected using a viral cytopathic assay. BAbs were measured by using an ELISA (Enzyme-linked immunosorbent assay).
Data has been presented as per planned analysis for integrated DB population which included all participants who received at least one dose of DB treatment in REFLEX study 27025 (NCT00404352). 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure at this time point.
Posted
Number
participants
Month 36
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
OG001
RNF 44 Mcg Once Weekly (Integrated DB Population)
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
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.
DB Safety Population 28981 (REFLEXION) included all the participants who discontinued DB treatment in REFLEX study 27025 (NCT00404352) and were enrolled in 28981 (REFLEXION) study and received at least one dose of DB treatment in this study. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Posted
Number
participants
Month 24 up to Month 36 (DB treatment period for study 28981 (REFLEXION)
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
Secondary
Time to Conversion to Clinically Definite Multiple Sclerosis (CDMS) Defined by Either a Second Attack or a Sustained Increase (Greater Than or Equal to 1.5 Points) in the Expanded Disability Status Scale (EDSS) Score up to Month 60
CDMS was defined by the occurrence of a second attack or relapse over 60 months in participants who presented with clinically isolated syndrome (CIS) accompanied by an abnormal magnetic resonance imaging (MRI) scan. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]) was calculated. Time to conversion to CDMS was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with CDMS.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
95% Confidence Interval
Cumulative % of participants with CDMS
Baseline (Day 1 of Study 27025) up to 60 Months
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Time to Confirmed Expanded Disability Status Scale (EDSS) Progression up to 60 Months
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. A confirmed EDSS progression was defined EDSS greater than or equal to 1.0 point confirmed during a visit performed 6 months later. Time to confirmed EDSS progression was represented by Kaplan-Meier estimates of the cumulative percentage (%) of participants with confirmed EDSS progression.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
% of participants with EDSS progression
Baseline (Day 1 of Study 27025) up to 60 Months
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Number of Combined Unique Active (CUA) Lesions, New Time Constant 2 (T2) Lesions, New Gadolinium Enhanced (Gd+) Lesions and New T1 Lesions Per Participant Per Scan at Month 60
Number of CUA lesions, new T2 lesions, new Gd+ Lesions and new T1 lesions were measured by using MRI scans.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
lesions
Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of RNF injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 84 participants were initially assigned to DB RNF 44 mcg thrice weekly and 49 participants were initially assigned to OL RNF 44 mcg thrice weekly (4 participants from DB converted to CDMS and switched to OL period over course of this study)
Secondary
Change From Baseline in Time Constant 1 (T1) Hypointense Volume, and Time Constant 2 (T2) Lesion Volume at Month 60
Change from baseline in lesion volume was measured by using MRI scans for T1 hypointense lesions and T2 lesions.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
mm^3
Baseline (Day 1 of Study 27025), Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of RNF injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 84 participants were initially assigned to DB RNF 44 mcg thrice weekly and 49 participants were initially assigned to OL RNF 44 mcg thrice weekly (4 participants from DB converted to CDMS and switched to OL period over course of this study)
Secondary
Percent Change From Baseline in Brain Volume at Month 60
Percent Change in brain volume was measured by using MRI scans.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure at this time point.
Posted
Mean
Standard Deviation
percent change
Baseline (Day 1 of Study 27025), Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Secondary
Percentage of Participants With Conversion to McDonald Multiple Sclerosis (MS) at Month 60
The McDonald criteria use dissemination in time and space established by MRI findings to provide a clinical diagnosis for MS. Dissemination in time is established by a new T2 or 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.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
percentage of participants
Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Change From Baseline in Paced Auditory Serial Addition Test 3 (PASAT-3) Score at Month 60
The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Score ranges from '0-60'. Higher scores reflect better neurological function and a positive change from baseline indicates improvement.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
units on a scale
Baseline (Day 1 of Study 27025), Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Percentage of Relapse-Free Participants at Month 60
A relapse was defined as the development of new or the exacerbation of existing neurological symptoms or signs, in the absence of fever, lasting for 24 hours and with a previous period for more than 30 days with a stable or an improving condition.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352).
Posted
Number
percentage of participants
Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) Score at Month 60
EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was calculated. The change in EDSS score at Month 60 was calculated as EDSS score at Month 60 minus EDSS score at baseline.
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
units on a scale
Baseline (Day 1 of Study 27025), Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Change From Baseline in Multiple Sclerosis Functional Composite (MSFC) Score at Month 60
The MSFC is a multidimensional clinical outcome measure which consists of three sub-tests; Timed 25-Foot Walk, 9-Hole Peg Test and Paced Auditory Serial Addition Test-3(PASAT-3). The Timed 25-Foot Walk is a quantitative measure of lower extremity function. The 9-Hole Peg Test is a quantitative measure of upper extremity (arm and hand) function. The PASAT is a measure of cognitive function that specifically assesses auditory information processing speed and flexibility, as well as calculation ability. Standardized results (Z-scores) of these sub-tests and the overall MSFC Z-score as an average of these three Z-scores was calculated. Higher Z-scores reflect better neurological function and a positive change from baseline indicates improvement. An increase in score indicates an improvement (range -3 to +3).
Data has been presented as per planned analysis for integrated ITT population which included all participants who were randomized in REFLEX study 27025 (NCT00404352). "n" signifies those participants who were evaluated for this measure at the specified time point for each arm group respectively.
Posted
Mean
Standard Deviation
Z-score
Baseline (Day 1 of Study 27025), Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Secondary
Numbers of Participants With Binding Antibodies (BAb) and Neutralizing Antibody (NAb) at Month 60
BAbs are all antibodies which are capable of binding to the RNF irrespective of their binding site. NAbs are defined as a subgroup of BAbs which bind to the active sites of the RNF and therefore neutralize its potency. NAbs were detected using a viral cytopathic assay. BAbs were measured by using an ELISA.
Data has been presented as per planned analysis for integrated DB population which included all participants who received at least one dose of DB treatment in REFLEX study 27025 (NCT00404352). 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure at this time point.
Posted
Number
participants
Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (Integrated DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
OG001
RNF 44 Mcg Once Weekly (Integrated DB Population)
Secondary
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) and AEs Leading to Treatment Discontinuation
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.
DB Safety Population 28981 (REFLEXION) included all the participants who discontinued DB treatment in REFLEX study 27025 (NCT00404352) and were enrolled in 28981 (REFLEXION) study and received at least one dose of DB treatment in this study. 'N' (number of participants analyzed) signifies those participants who were evaluable for this measure.
Posted
Number
participants
Month 24 up to Month 60
ID
Title
Description
OG000
Placebo/RNF 44 Mcg Thrice Weekly (DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
Time Frame
Month 24 to 60 for both DB safety population and OL safety population
Description
An adverse event (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.
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
Placebo/RNF 44 Mcg Thrice Weekly (DB Population)
Participants who were initially randomized in study 27025 (REFLEX) to the placebo treatment group were switched to single dose of fetal bovine serum [FBS]-free/human serum albumin [HSA]-free formulation of Interferon [IFN]-beta-1a (RNF) injection administered subcutaneously 3 times weekly at least 48 hours apart at a starting dose of 8.8 microgram (mcg) for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months or until conversion to clinically definite multiple sclerosis (CDMS) whichever occurs first.
7
84
69
84
EG001
RNF 44 Mcg Once Weekly (DB Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
7
117
97
117
EG002
RNF 44 Mcg Thrice Weekly (DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
9
99
84
99
EG003
Placebo/RNF 44 Mcg Thrice Weekly/OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
2
58
46
58
EG004
RNF 44 Mcg Once Weekly /OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
3
51
37
51
EG005
RNF 44 Mcg Thrice Weekly/OL RNF 44 Mcg Thrice Weekly
Participants after having converted to CDMS during study 28981 (REFLEXION), received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. The participants who were converted to CDMS in study 27025 (REFLEX) and were enrolled in this study continued receiving RNF 44 mcg three times weekly until 60 months.
4
46
36
46
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Abscess intestinal
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG0030 affected58 at risk
EG004
Diverticulitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Viral infection
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Appendicitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Endometritis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Peritonsillar abscess
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Salpingo-oophoritis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Cervix carcinoma stage 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Benign neoplasm of thyroid gland
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Malignant melanoma in situ
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0011 affected117 at risk
EG0021 affected99 at risk
EG003
Lumbar radiculopathy
Nervous system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Abortion missed
Pregnancy, puerperium and perinatal conditions
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Abortion spontaneous
Pregnancy, puerperium and perinatal conditions
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Foetal distress syndrome
Pregnancy, puerperium and perinatal conditions
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Angina stable
Cardiac disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Eye haemorrhage
Eye disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Enterovesical fistula
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Haematemesis
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Melaena
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Abdominal pain
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Abdominal pain upper
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0021 affected99 at risk
EG003
Foetal chromosome abnormality
Congenital, familial and genetic disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Vestibular disorder
Ear and labyrinth disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Fibula fracture
Injury, poisoning and procedural complications
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Post procedural fistula
Injury, poisoning and procedural complications
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Nephrolithiasis
Renal and urinary disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Renal colic
Renal and urinary disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Urticaria
Skin and subcutaneous tissue disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Appendicectomy
Surgical and medical procedures
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Venous insufficiency
Vascular disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0011 affected117 at risk
EG0020 affected99 at risk
EG003
Hypertension
Vascular disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Acute coronary syndrome
Cardiac disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Leukopenia
Blood and lymphatic system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0009 affected84 at risk
EG0012 affected117 at risk
EG0022 affected99 at risk
EG0030 affected58 at risk
EG0044 affected51 at risk
EG0051 affected46 at risk
Lymphopenia
Blood and lymphatic system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0004 affected84 at risk
EG0011 affected117 at risk
EG0025 affected99 at risk
EG003
Neutropenia
Blood and lymphatic system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0008 affected84 at risk
EG0013 affected117 at risk
EG0025 affected99 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0005 affected84 at risk
EG0011 affected117 at risk
EG0025 affected99 at risk
EG003
Diarrhoea
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0003 affected84 at risk
EG0018 affected117 at risk
EG0023 affected99 at risk
EG003
Toothache
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0005 affected84 at risk
EG0014 affected117 at risk
EG0024 affected99 at risk
EG003
Dyspepsia
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Nausea
Gastrointestinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Influenza like illness
General disorders
MedDRA Version 16.0
Non-systematic Assessment
EG00045 affected84 at risk
EG00139 affected117 at risk
EG00217 affected99 at risk
EG003
Injection site erythema
General disorders
MedDRA Version 16.0
Non-systematic Assessment
EG00017 affected84 at risk
EG0016 affected117 at risk
EG0028 affected99 at risk
EG003
Chills
General disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Fatigue
General disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Bronchitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0003 affected84 at risk
EG0015 affected117 at risk
EG0026 affected99 at risk
EG003
Cystitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Influenza
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0003 affected84 at risk
EG0018 affected117 at risk
EG0027 affected99 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG00012 affected84 at risk
EG00114 affected117 at risk
EG0029 affected99 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG00010 affected84 at risk
EG00111 affected117 at risk
EG00210 affected99 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0018 affected117 at risk
EG0023 affected99 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Blood creatine phosphokinase increased
Investigations
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0005 affected84 at risk
EG0017 affected117 at risk
EG0026 affected99 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Headache
Nervous system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG00011 affected84 at risk
EG00119 affected117 at risk
EG00216 affected99 at risk
EG003
Dizziness
Nervous system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Migraine
Nervous system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Anxiety
Psychiatric disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0003 affected84 at risk
EG0017 affected117 at risk
EG0024 affected99 at risk
EG003
Depression
Psychiatric disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0016 affected117 at risk
EG0022 affected99 at risk
EG003
Insomnia
Nervous system disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0001 affected84 at risk
EG0017 affected117 at risk
EG0024 affected99 at risk
EG003
Oropharyngeal pain
Respiratory, thoracic and mediastinal disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0000 affected84 at risk
EG0010 affected117 at risk
EG0020 affected99 at risk
EG003
Hypertension
Vascular disorders
MedDRA Version 16.0
Non-systematic Assessment
EG0005 affected84 at risk
EG0017 affected117 at risk
EG0021 affected99 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
Sponsor has the right to publish any results communication in connection with the study. The PI shall submit any communications including study results to the sponsor for review 30 working days prior to communication submission. The sponsor can request the PI to modify or delete any sponsor's proprietary information. If the PI refuses the modification, the submission shall be postponed for 60 days from PI refusal, to provide the sponsor the opportunity to file a patent or seek legal remedies.
Point of Contact
Title
Organization
Phone
Extension
Email
Merck KGaA Communication Center
Merck Serono, a division of Merck KGaA
+49-6151-72-5200
service@merckgroup.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
D000068556
Interferon beta-1a
Ancestor Terms
ID
Term
D016899
Interferon-beta
D007370
Interferon Type I
D007372
Interferons
D016207
Cytokines
D036341
Intercellular Signaling Peptides and Proteins
D010455
Peptides
D000602
Amino Acids, Peptides, and Proteins
D011506
Proteins
D001685
Biological Factors
Browse Leaves
Not provided
Browse Branches
Not provided
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
0 subjects
FG0050 subjects
51 subjects
FG00545 subjects
41 subjects
FG00535 subjects
10 subjects
FG00511 subjects
5 subjects
FG0044 subjects
FG0053 subjects
Lack of Efficacy
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG0041 subjects
FG0051 subjects
Randomized but not treated
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
Other
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG00311 subjects
FG0045 subjects
FG0056 subjects
31.4
± 8.3
55
BG003188
Greater than or equal to 30 years
Title
Measurements
BG00066
BG00176
BG00272
BG003214
78
BG003248
Male
BG00051
BG00154
BG00249
BG003154
0
BG0031
White
Title
Measurements
BG000133
BG001141
BG002127
BG003401
Hazard Ratio (HR)
0.573
2-Sided
95
0.391
0.839
Superiority or Other
OG001
OG002
Log Rank
0.941
Hazard Ratio (HR)
0.993
2-Sided
95
0.654
1.510
Superiority or Other
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG0007.5
OG00111.8
OG00213.2
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
Log Rank
0.205
95
Superiority or Other
OG000
OG001
Log Rank
0.263
95
Superiority or Other
OG001
OG002
Log Rank
0.629
95
Superiority or Other
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000124
OG001133
OG002114
Title
Denominators
Categories
CUA Lesions
Title
Measurements
OG0001.02± 1.85
OG0011.83± 3.317
OG0021.63± 5.947
New T2 Lesions
Title
Measurements
OG0000.83± 1.545
OG0011.39± 2.573
OG0021.19± 4.217
New Gd+ Lesions
Title
Measurements
OG0000.17± 0.506
OG0010.40± 1.354
OG0020.41± 1.754
New T1 Lesions
Title
Measurements
OG0000.69± 1.721
OG0011.09± 2.482
OG0020.91± 4.143
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
T1 lesion volume at Baseline (n=171,175,171)
Title
Measurements
OG000670.3± 1054.1
OG001774.8± 1288.0
OG002675.0± 1049.9
T1 lesion volume Change: Month 36(n=124,133,114)
Title
Measurements
OG000303.2± 1034.6
OG001272.0± 921.4
OG002133.3± 763.5
T2 lesion volume at Baseline (n=171,175,171)
Title
Measurements
OG0003334.9± 3990.4
OG0013853.1± 4716.7
OG0023110.5± 3410.7
T2 lesion volume Change: Month 36(n=124,133,114)
Title
Measurements
OG000-3.8± 2101.8
OG001-56.9± 2436.3
OG002-398.1± 1415.4
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000120
OG001132
OG002112
Title
Denominators
Categories
Title
Measurements
OG000-1.02± 1.248
OG001-0.86± 1.073
OG002-1.14± 1.321
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00084.2
OG00176.0
OG00266.7
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Baseline (n=171,175,171)
Title
Measurements
OG0000.0358± 0.8787
OG001-0.0909± 1.1223
OG0020.0031± 1.1387
Change at Month 36 (n=123,135,118)
Title
Measurements
OG0000.3483± 0.6949
OG0010.5044± 0.7588
OG0020.4515± 0.9164
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00042.7
OG00158.3
OG00251.5
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Baseline (n=171,175,171)
Title
Measurements
OG0001.53± 0.77
OG0011.50± 0.72
OG0021.51± 0.83
Change at Month 36 (n=120,136,116)
Title
Measurements
OG000-0.21± 0.93
OG001-0.11± 0.96
OG002-0.09± 0.90
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 36 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
MFSC score at Baseline (n=171,175,171)
Title
Measurements
OG0000.0352± 0.5844
OG0010.0071± 0.6653
OG002-0.0575± 0.6226
Change at Month 36 (n=123,135,118)
Title
Measurements
OG0000.1993± 0.4863
OG0010.2529± 0.5794
OG0020.3074± 0.6071
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first.
OG002
RNF 44 Mcg Thrice Weekly (Integrated DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first.
Units
Counts
Participants
OG000118
OG001131
OG002118
Title
Denominators
Categories
BAb-
Title
Measurements
OG00077
OG00197
OG00288
BAb+
Title
Measurements
OG00041
OG00134
OG00230
NAb-
Title
Measurements
OG000100
OG001109
OG00299
NAb+
Title
Measurements
OG00018
OG00122
OG00219
OG001
RNF 44 Mcg Once Weekly (DB Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first.
OG002
RNF 44 Mcg Thrice Weekly (DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 36 months or until conversion to CDMS whichever occurs first.
Units
Counts
Participants
OG00084
OG001117
OG00299
Title
Denominators
Categories
AEs
Title
Measurements
OG00079
OG00167
OG00245
SAEs
Title
Measurements
OG0003
OG0012
OG0024
AEs leading to discontinuation
Title
Measurements
OG0002
OG0010
OG0022
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00044.6(36.6 to 52.6)
OG00140.7(32.8 to 48.6)
OG00239.2(30.8 to 47.6)
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00011.0
OG00118.7
OG00218.4
OG001
RNF 44 Mcg Once Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 117 participants were initially assigned to DB RNF 44 mcg thrice weekly and 25 participants were initially assigned to OL RNF 44 mcg thrice weekly (10 participants from DB converted to CDMS and switched to OL period over course of this study)
OG002
RNF 44 Mcg Thrice Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 99 participants were initially assigned to DB RNF 44 mcg thrice weekly and 28 participants were initially assigned to OL RNF 44 mcg thrice weekly (6 participants from DB converted to CDMS and switched to OL period over course of this study)
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
CUA Lesions (n=102, 121, 110)
Title
Measurements
OG0001.46± 3.394
OG0011.60± 3.542
OG0021.94± 4.803
New T2 Lesions (n=102, 121, 110)
Title
Measurements
OG0001.17± 2.576
OG0011.17± 2.628
OG0021.35± 3.284
New Gd+ Lesions (n=102, 121, 110)
Title
Measurements
OG0000.24± 0.823
OG0010.36± 1.225
OG0020.48± 1.618
New T1 Lesions (n=102, 120, 110)
Title
Measurements
OG0000.57± 1.656
OG0010.69± 1.659
OG0020.71± 1.917
OG001
RNF 44 Mcg Once Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 117 participants were initially assigned to DB RNF 44 mcg thrice weekly and 25 participants were initially assigned to OL RNF 44 mcg thrice weekly (10 participants from DB converted to CDMS and switched to OL period over course of this study)
OG002
RNF 44 Mcg Thrice Weekly (ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received OL study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months. 99 participants were initially assigned to DB RNF 44 mcg thrice weekly and 28 participants were initially assigned to OL RNF 44 mcg thrice weekly (6 participants from DB converted to CDMS and switched to OL period over course of this study)
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
T1 lesion volume at Baseline (n=171,175,171)
Title
Measurements
OG000670.3± 1054.1
OG001774.8± 1288.0
OG002675.0± 1049.9
Change at Month 60 (n=102,120,110)
Title
Measurements
OG000415.0± 1080.3
OG001412.3± 1020.8
OG002261.8± 1006.1
T2 lesion volume at Baseline (n=171,175,171)
Title
Measurements
OG0003334.9± 3990.4
OG0013853.1± 4716.7
OG0023110.5± 3410.7
Change at Month 60 (n=102,121,110)
Title
Measurements
OG000119.4± 2225.2
OG00125.0± 2827.1
OG002-188.5± 2576.1
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG00098
OG001120
OG002110
Title
Denominators
Categories
Title
Measurements
OG000-1.82± 1.494
OG001-1.54± 1.378
OG002-2.03± 1.644
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00084.2
OG00182.9
OG00272.5
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Baseline (n=171, 175, 171)
Title
Measurements
OG0000.0358± 0.8787
OG001-0.0909± 1.1223
OG0020.0031± 1.1387
Change at Month 60 (n=112, 132, 118)
Title
Measurements
OG0000.4109± 0.6844
OG0010.4785± 0.9886
OG0020.4608± 0.8630
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Title
Measurements
OG00034.5
OG00145.1
OG00240.9
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
Baseline (n=171,175,171)
Title
Measurements
OG0001.53± 0.77
OG0011.50± 0.72
OG0021.51± 0.83
Change at Month 60 (n=111,133,117)
Title
Measurements
OG000-0.11± 0.94
OG001-0.01± 1.01
OG0020.04± 1.02
OG001
RNF 44 Mcg Once Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
OG002
RNF 44 Mcg Thrice Weekly (Integrated ITT Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first. After having converted to CDMS, participants received open-label (OL) study treatment with RNF. Single dose of RNF injection administrated subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and finally 44 mcg until 60 months.
Units
Counts
Participants
OG000171
OG001175
OG002171
Title
Denominators
Categories
MFSC score at Baseline (n=171,175,171)
Title
Measurements
OG0000.0352± 0.5844
OG0010.0071± 0.6653
OG002-0.0575± 0.6226
Change at Month 60 (n=112,132,132)
Title
Measurements
OG0000.2290± 0.4824
OG0010.2213± 0.5602
OG0020.2192± 0.6229
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
OG002
RNF 44 Mcg Thrice Weekly (Integrated DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
Units
Counts
Participants
OG000115
OG001130
OG002115
Title
Denominators
Categories
BAb-
Title
Measurements
OG00089
OG00199
OG002100
BAb+
Title
Measurements
OG00025
OG00130
OG00215
BAb (Missing)
Title
Measurements
OG0001
OG0011
OG0020
NAb-
Title
Measurements
OG00097
OG001110
OG002102
NAb+
Title
Measurements
OG00018
OG00120
OG00213
OG001
RNF 44 Mcg Once Weekly (DB Population)
Single dose of RNF injection administered subcutaneously once weekly plus 2 matching placebo doses at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.
OG002
RNF 44 Mcg Thrice Weekly (DB Population)
Single dose of RNF injection administered subcutaneously three times weekly at least 48 hours apart at a starting dose of 8.8 mcg for first 2 weeks followed by 22 mcg for next 2 weeks and then 44 mcg until 60 months or until conversion to CDMS whichever occurs first.