A Study of Efficacy and Safety of M2951 in Participants W... | NCT02975349 | Trialant
NCT02975349
Sponsor
EMD Serono Research & Development Institute, Inc.
Status
Terminated
Last Update Posted
May 14, 2025Actual
Enrollment
267Actual
Phase
Phase 2
Conditions
Relapsing-remitting Multiple Sclerosis
Interventions
Evobrutinib
Evobrutinib
Evobrutinib
Placebo
Tecfidera
Countries
Bulgaria
Czechia
Poland
Russia
Serbia
Slovakia
Spain
Ukraine
Protocol Section
Identification Module
NCT ID
NCT02975349
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
MS200527-0086
Secondary IDs
ID
Type
Description
Link
2016-001448-21
EudraCT Number
Brief Title
A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis
Official Title
A Randomized, Double-Blind, Placebo-Controlled Phase II Study of M2951 With a Parallel, Open-Label, Active Control Group (Tecfidera), in Patients With Relapsing Multiple Sclerosis to Evaluate Efficacy, Safety, Tolerability, Pharmacokinetics, and Biological Activity.
Acronym
Not provided
Organization
EMD SeronoINDUSTRY
Status Module
Record Verification Date
May 2025
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Results from the EVOLUTION clinical trials showed evobrutinib did not meet its primary endpoint of annualized relapse rate for up to 156 weeks compared to oral teriflunomide in both studies.
Expanded Access Info
No
Start Date
Mar 7, 2017Actual
Primary Completion Date
Jan 24, 2018Actual
Completion Date
Apr 2, 2024Actual
First Submitted Date
Nov 23, 2016
First Submission Date that Met QC Criteria
Nov 23, 2016
First Posted Date
Nov 29, 2016Estimated
Results Waived
Not provided
Results First Submitted Date
Jan 13, 2021
Results First Submitted that Met QC Criteria
Jan 13, 2021
Results First Posted Date
Feb 5, 2021Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Jan 14, 2019
Certification/Extension First Submitted that Passed QC Review
Jan 14, 2019
Certification/Extension First Posted Date
Jan 17, 2019Actual
Last Update Submitted Date
May 13, 2025
Last Update Posted Date
May 14, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
EMD Serono Research & Development Institute, Inc.INDUSTRY
Collaborators
Name
Class
Merck KGaA, Darmstadt, Germany
INDUSTRY
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
The aim of this protocol is to find out about the safety and effectiveness of M2951 in participants with relapsing multiple sclerosis. Participants were placed into 1 of 3 groups to receive M2951, placebo or tecfidera for 24 weeks. After 24 weeks, the participants on placebo were given M2951.
Detailed Description
Not provided
Conditions Module
Conditions
Relapsing-remitting Multiple Sclerosis
Keywords
M2951
Relapsing Multiple Sclerosis
Bruton's Tyrosine Kinase inhibitor
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 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
267Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Placebo then Evobrutinib 25 mg QD (Period 2)
Experimental
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
Drug: Evobrutinib
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Drug: Evobrutinib
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Drug: Evobrutinib
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Experimental
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Drug: Evobrutinib
Tecfidera (Period 1, 2 and 3)
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Evobrutinib
Drug
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Total Number of Gadolinium-Enhancing T1 Lesions
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Week 12 to Week 24
Secondary Outcomes
Measure
Description
Time Frame
Annualized Relapse Rate (ARR) at Week 24
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
Participants with a diagnosis of relapsing multiple sclerosis (may include participants with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed relapses provided they meet the other criteria) in accordance with revised McDonald criteria for MS and Lublin and Reingold
Male or female aged 18 to 65 years
One or more documented relapses within the 2 years before Screening with either: a) One relapse which occurred within the last year prior to randomization or b) the presence of at least 1 gadolinium-positive (Gd+) T1 lesion within 6 months prior to randomization would make the patient eligible.
Expanded Disability Status Scale score of 0 to 6 at Baseline
Women of childbearing potential must use a supplementary barrier method together with a highly effective method of contraception (according to International Council for Harmonisation [ICH] guidance M3[R2]) for 4 weeks prior to randomization, throughout the trial, and for 90 days after the last dose of IMP.
Signed and dated informed consent (participant must be able to understand the informed consent) indicating that the participant has been informed of all the pertinent aspects of the trial prior to enrolment and will comply with the requirements of the protocol.
Exclusion Criteria:
Progressive MS
Disease duration > 15 years in participants with EDSS of 2 or less
Use of the following, as determined in the protocol ; rituximab, ocrelizumab, mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg, natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis, immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic glucocorticoids, teriflunomide
Exposure to Tecfidera within 6 months prior to randomization
Any allergy, contraindication, or inability to tolerate Tecfidera
Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30 days prior to randomization
Inability to comply with MRI scanning
Immunologic disorder other than MS, with the exception of secondary well-controlled diabetes or thyroid disorder, or any other condition requiring oral, IV, intramuscular, or intra-articular corticosteroid therapy
Vaccination with live or live-attenuated virus vaccine within 1 month prior to Screening
Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its incipients
Active, clinically significant viral, bacterial, or fungal infection, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3 or more of the same type of infection in a 12-month rolling period). Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary.
History of or positive testing for human immunodeficiency virus (HIV), hepatitis C (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg) (+) and/or hepatitis B core total, and/or immunoglobulin M (IgM) antibody (+) at Screening.
The participant: • Has a history of or current diagnosis of active tuberculosis (TB) or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.
Indeterminate QuantiFERON®
Participants with current household contacts with active TB will also be excluded
History of splenectomy or any major surgery within 2 months prior to Screening
History of myocardial infarction or cerebrovascular event as per the protocol
History of attempted suicide within 6 months prior to Screening or a positive response to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)
An episode of major depression within the last 6 months prior to Screening
On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily aspirin for cardioprotection and treatment of Tecfidera induced flushing
History of cancer, except adequately treated basal cell or squamous cell carcinoma of the skin
Breastfeeding/lactating or pregnant women
Participation in any investigational drug trial within 1 month or 5 half-lives of the investigational drug, whichever is longest, prior to Screening
Participants currently receiving (or unable to stop using prior to receiving the first dose of IMP) medications or herbal supplements known to be potent inhibitors of cytochrome P450 3A (CYP3A)
History of or current alcohol or substance abuse
Clinically significant abnormality on electrocardiogram or screening chest X-ray
Clinically significant laboratory abnormality
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
65 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Medical Responsible
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Montalban X, Arnold DL, Weber MS, Staikov I, Piasecka-Stryczynska K, Willmer J, Martin EC, Dangond F, Syed S, Wolinsky JS; Evobrutinib Phase 2 Study Group. Placebo-Controlled Trial of an Oral BTK Inhibitor in Multiple Sclerosis. N Engl J Med. 2019 Jun 20;380(25):2406-2417. doi: 10.1056/NEJMoa1901981. Epub 2019 May 10.
Per company policy and with respect to the principles set forth by the International Federation of Pharmaceutical Manufacturers and Associations (IFPMA), the European Federation of Pharmaceutical Industries and Associations (EFPIA), the Pharmaceutical Research and Manufacturers of America (PhRMA), the Declaration of Helsinki, and applicable laws and regulations , we inform the public about the designs and results of our clinical trials in a timely and balanced manner, regardless of the outcome. We are committed to enhancing public health through responsible sharing of clinical trial data in a manner that is consistent with: safeguarding the privacy of patients; respecting the integrity of national regulatory systems; and maintaining incentives for investment in biomedical research.
Types
Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Analytic Code
Time Frame
Within six months after the occurrence of an approval of a new product or a new indication for an approved product in both the European Union and the United States after January 1, 2014 If approval of a product is not sought, Merck shall make publicly available such data within eighteen months after the trial completion date. Data will not be shared for products and indications approved prior to January 1, 2014
Access Criteria
Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researcher qualifications and legitimacy of the research purpose.
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
FG001
Placebo Then Evobrutinib 25 mg QD (Period 2)
Periods
Title
Milestones
Reasons Not Completed
Active Treatment Period (24 Weeks)
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
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot
Yes
No
No
Study Protocol
Jul 6, 2023
Apr 1, 2025
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Germany
United States
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
InvestigatorOutcomes Assessor
Active Comparator
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Drug: Tecfidera
Placebo
Placebo Comparator
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
Drug: Placebo
Placebo + Evobrutinib 25 mg QD (Period 3)
Experimental
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Drug: Evobrutinib
Evobrutinib 75 mg BID (Period 1, 2 and 3)
M2951
Evobrutinib
Drug
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Placebo + Evobrutinib 25 mg QD (Period 3)
Placebo then Evobrutinib 25 mg QD (Period 2)
M2951
Evobrutinib
Drug
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Evobrutinib 75 mg QD (Period 1, 2 and 3)
M2951
Placebo
Drug
Placebo were administered for 24 weeks in active treatment period.
Placebo
Tecfidera
Drug
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Tecfidera (Period 1, 2 and 3)
Week 24
Qualified Relapse-Free Status at Week 24
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Week 24
Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Baseline, Week 24
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
Baseline up to Safety Follow-up (Week 52)
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator.
Baseline up to Safety Follow-up (Week 52)
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Hematology, biochemistry, and urinalysis values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). For the hematology and biochemistry parameters, participants with a value grade 3 or higher were reported. For the urinalysis parameters, participants with a value grade 3 or higher, or a value >= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.
Baseline up to Safety Follow-up (Week 52)
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Baseline (Day 1), Weeks 4, 16, and 24
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Week 48
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Baseline (Day 1), Weeks 4, 16, and 24
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
Baseline (Week 25), Week 48
Absolute Concentration of B Cells (Active Treatment Period)
Absolute concentration of B Cells are reported.
Baseline (Day 1), Weeks 4, and 24
Absolute Concentration of B Cells (Blinded Extension Period)
Absolute concentration of B Cells were reported.
Weeks 48 and 52
Change From Baseline in Absolute B Cells (Active Treatment Period)
Change from baseline in absolute B cells are reported.
Baseline (Day 1), Weeks 4 and 24
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Change from baseline in absolute B cells are reported.
Baseline (Week 25), Weeks 48 and 52
Total Number of New Gadolinium-positive (Gd+) T1 Lesions
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Week 12 to 24
Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Week 12 to Week 24
Total Number of New or Enlarging T2 Lesions
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Week 12 to Week 24
Change From Baseline in Volume of T2 Lesions at Week 24
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.
Baseline, Week 24
Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Baseline, Week 24
Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Week 48
Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Week 48
Annualized Relapse Rate (ARR)
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
Week 0 to Week 48
Qualified Relapse-free Status
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status were reported.
Week 25 to Week 48
Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
Week 24, Week 48
Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.
Week 24 to Week 48
Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Week 24, Week 48
Change From Week 24 in Volume of T2 Lesions at Week 48
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.
Week 24, Week 48
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans.
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
OLE Period: Annualized Relapse Rate (ARR)
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
OLE Period: Percentage of Participants With Qualified Relapse-Free Status
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status from OLE Baseline (BE period Week 48) up to Week 336 were reported.
OLE Baseline (BE period Week 48) up to OLE Week 336
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
OLE Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
OLE Baseline (BE period Week 48) up to OLE Week 336
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. Number of participants with clinically significant change from baseline in vital signs were reported. Clinical Significance was decided by the investigator.
OLE Baseline (BE period Week 48) up to OLE Week 336
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory parameters included hematology, biochemistry, and urinalysis. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator.
OLE Baseline (BE period Week 48) up to OLE Week 336
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECGs)
ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in ECG were reported. Clinical Significance was decided by the investigator.
OLE Baseline (BE period Week 48) up to OLE Week 336
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288
Dupnitsa
2600
Bulgaria
Research Site 1
Pleven
5800
Bulgaria
Research Site 2
Pleven
5800
Bulgaria
Research Site
Rousse
7002
Bulgaria
Research Site
Sofia
1142
Bulgaria
Research Site
Sofia
1309
Bulgaria
Research Site
Sofia
1336
Bulgaria
Research Site
Sofia
1407
Bulgaria
Research Site
Sofia
1431
Bulgaria
Research Site
Sofia
1606
Bulgaria
Research Site
Sofia
1797
Bulgaria
Research Site
Brno
656 91
Czechia
Research Site
Hradec Králové
500 05
Czechia
Research Site
Hradec Králové
50003
Czechia
Research Site
Jihlava
58633
Czechia
Research Site
Prague
150 06
Czechia
Research Site
Teplice
41529
Czechia
Research Site
Bydgoszcz
85-654
Poland
Research Site
Katowice
40-595
Poland
Research Site
Katowice
40-650
Poland
Research Site
Lodz
90-324
Poland
Research Site
Lublin
20-605
Poland
Research Site
Oświęcim
32-600
Poland
Research Site
Plewiska
62-064
Poland
Research Site
Poznan
61-853
Poland
Research Site
Rzeszów
35-055
Poland
Research Site
Warsaw
01-697
Poland
Research Site
Kazan'
420021
Russia
Research Site
Krasnoyarsk
660037
Russia
Research Site
Krasnoyarsk
660049
Russia
Research Site
Moscow
129128
Russia
Research Site
Novosibirsk
630102
Russia
Research Site
Perm
614000
Russia
Research Site
Saransk
430032
Russia
Research Site
Belgrade
11000
Serbia
Research Site
Kragujevac
34000
Serbia
Research Site
Niš
18000
Serbia
Research Site
Užice
31000
Serbia
Research Site
Banská Bystrica
97404
Slovakia
Research Site
Bratislava
85101
Slovakia
Research Site
Dubnica nad Váhom
01841
Slovakia
Research Site
A Coruña
15006
Spain
Research Site
Barcelona
08003
Spain
Research Site
Barcelona
08035
Spain
Research Site
Chernivtsi
58018
Ukraine
Research Site
Ivano-Frankivsk
76008
Ukraine
Research Site
Kharkiv
61058
Ukraine
Research Site
Kharkiv
61068
Ukraine
Research Site
Kharkiv
61103
Ukraine
Research Site
Kyiv
01601
Ukraine
Research Site
Kyiv
03110
Ukraine
Research Site
Lviv
79010
Ukraine
Research Site
Poltava
36011
Ukraine
Research Site
Zaporizhzhia
69035
Ukraine
Research Site
Zaporizhzhia
69600
Ukraine
Arnold DL, Elliott C, Martin EC, Hyvert Y, Tomic D, Montalban X. Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial. Neurology. 2024 Mar 12;102(5):e208058. doi: 10.1212/WNL.0000000000208058. Epub 2024 Feb 9.
Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Le Bolay C, Kao AH, Guehring H. Characterisation of the safety profile of evobrutinib in over 1000 patients from phase II clinical trials in multiple sclerosis, rheumatoid arthritis and systemic lupus erythematosus: an integrated safety analysis. J Neurol Neurosurg Psychiatry. 2023 Jan;94(1):1-9. doi: 10.1136/jnnp-2022-328799. Epub 2022 Nov 23.
Bar-Or A, Cross AH, Cunningham AL, Hyvert Y, Seitzinger A, Guhring H, Drouin EE, Alexandri N, Tomic D, Montalban X. Antibody response to SARS-CoV-2 vaccines in patients with relapsing multiple sclerosis treated with evobrutinib: A Bruton's tyrosine kinase inhibitor. Mult Scler. 2023 Oct;29(11-12):1471-1481. doi: 10.1177/13524585231192460. Epub 2023 Aug 25.
Montalban X, Wallace D, Genovese MC, Tomic D, Parsons-Rich D, Bolay CL, Kao AH, Guehring H. A plain language summary of what clinical studies can tell us about the safety of evobrutinib - a potential treatment for multiple sclerosis. Neurodegener Dis Manag. 2023 Aug;13(4):207-213. doi: 10.2217/nmt-2023-0003. Epub 2023 Jun 22.
Medical Information Location Map - Med Info Contacts
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
FG002
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
FG003
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
FG004
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
FG005
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
FG006
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
FG00054 subjects
FG0010 subjects
FG0020 subjects
FG00352 subjects
FG00453 subjects
FG00554 subjects
FG00654 subjects
Safety Analysis Set
Safety analysis set included all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
FG00054 subjects
FG0010 subjects
FG0020 subjects
FG00352 subjects
FG00453 subjects
FG00554 subjects
FG00654 subjects
COMPLETED
FG00049 subjects
FG0010 subjects
FG0020 subjects
FG00347 subjects
FG00448 subjects
FG00548 subjects
FG00652 subjects
NOT COMPLETED
FG0005 subjects
FG0010 subjects
FG0020 subjects
FG0035 subjects
FG0045 subjects
FG0056 subjects
FG0062 subjects
Type
Comment
Reasons
Withdrawal by Subject
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0033 subjects
FG0043 subjects
FG0050 subjects
FG0060 subjects
Lost to Follow-up
FG0001 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Adverse Event
FG0004 subjects
FG0010 subjects
FG0020 subjects
FG0032 subjects
FG004
Blinded Extension Period (24 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG00149 subjects
FG0020 subjects
FG00347 subjects
FG00448 subjects
FG00548 subjects
FG00652 subjects
COMPLETED
FG0000 subjects
FG00142 subjects
FG0020 subjects
FG00343 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0017 subjects
FG0020 subjects
FG0034 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0011 subjects
FG0020 subjects
FG003
Open-label Extension Period (336 Weeks)
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG00239 subjects
FG00339 subjects
FG00442 subjects
FG00544 subjects
FG00649 subjects
COMPLETED
FG0000 subjects
FG0010 subjects
FG00228 subjects
FG00325 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG00211 subjects
FG00314 subjects
FG004
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0023 subjects
FG003
Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
BG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
BG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
BG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
BG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
BG005
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG00053
BG00150
BG00251
BG00353
BG00454
BG005261
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
BG00041.6± 10.77
BG00142.4± 9.37
BG00242.9± 10.07
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG00039
BG00132
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0001
BG0011
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
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
Total Number of Gadolinium-Enhancing T1 Lesions
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
Lesions
Week 12 to Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG003
Title
Denominators
Categories
Title
Measurements
OG0003.85± 5.436
OG0014.06± 8.024
OG0021.69± 4.693
OG003
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
OG001
Negative Binomial model
0.2947
Lesion rate ratio
1.45
2-Sided
95
0.72
2.91
Superiority
OG000
OG002
Negative Binomial model
0.0015
Secondary
Annualized Relapse Rate (ARR) at Week 24
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
The modified ITT (mITT) analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
95% Confidence Interval
relapses per year
Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
Qualified Relapse-Free Status at Week 24
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status at week 24 were reported. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline MRI assessment.
Posted
Number
95% Confidence Interval
percentage of participants
Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS). As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
Units on a scale
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
Posted
Count of Participants
Participants
Baseline up to Safety Follow-up (Week 52)
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Placebo Then Evobrutinib 25 mg QD (Period 2)
Secondary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in vital signs and ECG were reported. Clinical Significance was decided by the investigator.
The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
Posted
Count of Participants
Participants
Baseline up to Safety Follow-up (Week 52)
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG002
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Secondary
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Hematology, biochemistry, and urinalysis values were graded with National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03 toxicity grades (where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life threatening and Grade 5 = death). For the hematology and biochemistry parameters, participants with a value grade 3 or higher were reported. For the urinalysis parameters, participants with a value grade 3 or higher, or a value >= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.
The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.
Posted
Count of Participants
Participants
Baseline up to Safety Follow-up (Week 52)
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG002
Secondary
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Posted
Mean
Standard Deviation
Gram per Liter
Baseline (Day 1), Weeks 4, 16, and 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Results reported are for blinded extension period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
Gram per Liter
Week 48
ID
Title
Description
OG000
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Posted
Mean
Standard Deviation
Gram per Liter
Baseline (Day 1), Weeks 4, 16, and 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure. Results reported are for blinded extension period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
Gram per Liter
Baseline (Week 25), Week 48
ID
Title
Description
OG000
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Absolute Concentration of B Cells (Active Treatment Period)
Absolute concentration of B Cells are reported.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Posted
Mean
Standard Deviation
cells per micro-liter
Baseline (Day 1), Weeks 4, and 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Absolute Concentration of B Cells (Blinded Extension Period)
Absolute concentration of B Cells were reported.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points. Results reported are for blinded extension period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
cells per micro-liter
Weeks 48 and 52
ID
Title
Description
OG000
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Secondary
Change From Baseline in Absolute B Cells (Active Treatment Period)
Change from baseline in absolute B cells are reported.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points.
Posted
Mean
Standard Deviation
cells per micro-liter
Baseline (Day 1), Weeks 4 and 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Change from baseline in absolute B cells are reported.
The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, "Overall Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure and "Number Analyzed" signified those participants who were evaluable for the specified category at given time points. Results reported are for blinded extension period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
cells per micro-liter
Baseline (Week 25), Weeks 48 and 52
ID
Title
Description
OG000
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Secondary
Total Number of New Gadolinium-positive (Gd+) T1 Lesions
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
Modified Intent-To-Treat (mITT) analysis set included participants who belong to both Intent To Treat (ITT, consisted all participants who randomly allocated to a treatment, based on the intention to treat "as randomized" principle) and safety analysis sets (consisted all participants who receive at least 1 dose of trial treatment), and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
Lesions
Week 12 to 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
Analysis of Gadolinium-positive T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
Lesions
Week 12 to Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Total Number of New or Enlarging T2 Lesions
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
Lesions
Week 12 to Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Baseline in Volume of T2 Lesions at Week 24
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment. Here, "Number of Participants Analyzed" signifies those participants who were evaluable for this outcome measure.
Posted
Mean
Standard Deviation
cubic centimeter (cc)
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans. As per planned analysis, Tecfidera treatment group was not included in inferential analysis.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
Standard Deviation
cc
Baseline, Week 24
ID
Title
Description
OG000
Placebo (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Mean
Standard Deviation
Lesions
Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Mean
Standard Deviation
Lesions
Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Annualized Relapse Rate (ARR)
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
mITT analysis set consists of all participants who belong to both the ITT and safety analysis sets, and who have at least one baseline and one post-baseline magnetic resonance imaging (MRI) assessment.
Posted
Mean
95% Confidence Interval
relapses per year
Week 0 to Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
Qualified Relapse-free Status
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status were reported.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Number
percentage of participants
Week 25 to Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Mean
Standard Deviation
Units on a scale
Week 24, Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period. Here, "Number of Participants Analyzed" signified those participants who were evaluable for this outcome measure.
Posted
Mean
Standard Deviation
Lesions
Week 24 to Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Mean
Standard Deviation
cc
Week 24, Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
Change From Week 24 in Volume of T2 Lesions at Week 48
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.
mITT BE analysis set included all participants who belonged to the mITT analysis set with an MRI assessment during the 24-week blinded extension period.
Posted
Mean
Standard Deviation
cc
Week 24, Week 48
ID
Title
Description
OG000
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
OLE Period: Total Number of Gadolinium-Enhancing T1 Lesions
Analysis of T1-Gadolinium enhancing lesions was done using magnetic resonance imaging (MRI) scans.
modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed= participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
Lesions
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Secondary
OLE Period: Annualized Relapse Rate (ARR)
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days.
modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Here, "Number analyzed" signifies those participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Mean
95% Confidence Interval
relapses per year
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
OLE Period: Percentage of Participants With Qualified Relapse-Free Status
A qualifying relapse is defined as new, worsening or recurrent neurological symptoms attributed to Multiple Sclerosis (MS) that last for at least 24 hours without fever or infection, or adverse reaction to prescribed medication, preceded by a stable or improving neurological status of at least 30 days. Percentage of participants with qualified relapse-free status from OLE Baseline (BE period Week 48) up to Week 336 were reported.
modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Number
percentage of participants
OLE Baseline (BE period Week 48) up to OLE Week 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
OLE Period: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 96, 144, 192, 240, 288 and 336
The EDSS is an ordinal clinical rating scale in half-point increments. It assesses the following eight functional systems, areas of the central nervous system that control bodily functions: Pyramidal (ability to walk), Cerebellar (coordination), Brain stem (speech and swallowing), Sensory (touch and pain), Bowel and bladder functions, Visual, Mental, Other (includes any other neurological findings due to Multiple Sclerosis [MS]). EDSS overall score ranging from 0 (normal) to 10 (death due to MS).
modified ITT OLE Analysis Set (mITT-OLE) Analysis Set: participants randomly allocated to a treatment who belong to Safety OLE Analysis Set, and who have at least 1 Magnetic Resonance Imaging (MRI) assessment on or after OLE Week 0. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
units on a scale
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240, 288 and 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Secondary
OLE Period: Number of Participants With Treatment-emergent Adverse Events (TEAEs)
An adverse event (AE) was defined as any untoward medical occurrence in a participant which does not necessarily have a causal relationship with the study drug. An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent adverse events are defined as any adverse event with a start date on or after the date of first dose and within 28 days after the date of last dose in the study. TEAEs include both Serious TEAEs and non-serious TEAEs.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Count of Participants
Participants
OLE Baseline (BE period Week 48) up to OLE Week 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Secondary
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Vital signs, including semi supine blood pressure, pulse rate, respiratory rate, weight, and oral temperature were assessed. Number of participants with clinically significant change from baseline in vital signs were reported. Clinical Significance was decided by the investigator.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Count of Participants
Participants
OLE Baseline (BE period Week 48) up to OLE Week 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
Laboratory parameters included hematology, biochemistry, and urinalysis. Number of participants with clinically significant change from baseline in laboratory parameters were reported. Clinical Significance was decided by the investigator.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Count of Participants
Participants
OLE Baseline (BE period Week 48) up to OLE Week 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
OLE Period: Number of Participants With Clinically Significant Changes From Baseline in Electrocardiograms (ECGs)
ECG parameters included rhythm, ventricular rate, PR interval, QRS duration, and QT interval. Number of participants with clinically significant change from baseline in ECG were reported. Clinical Significance was decided by the investigator.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Count of Participants
Participants
OLE Baseline (BE period Week 48) up to OLE Week 336
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
OLE Period: Absolute Concentrations of Immunoglobulin (Ig) Levels
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
Gram per Liter
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Secondary
OLE Period: Change From Baseline in Immunoglobulin (Ig) Levels
Change from baseline in the serum levels of IgG, IgA, IgM were assessed.
The Safety OLE Analysis Set included all participants who receive at least 1 dose of Evobrutinib during the OLE. Overall Number of Participants Analyzed= Participants evaluable for this outcome measure and Number analyzed = participants who were evaluable for the specified category. Results reported are for OLE period only and no participants took placebo during this period.
Posted
Mean
Standard Deviation
Gram per Liter
OLE Baseline (BE period Week 48), OLE Weeks 96, 144, 192, 240 and 288
ID
Title
Description
OG000
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Time Frame
Baseline up to Safety Follow up of blinded extension period (Week 52); OLE Baseline (BE period Week 48) up to OLE Week 336
Description
Active treatment period and BE period: MedDRA version 21.0; OLE Period: MedDRA version 26.1
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 (Period 1)
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
0
54
2
54
14
54
EG001
Placebo Then Evobrutinib 25 mg QD (Period 2)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
0
49
0
49
9
49
EG002
Evobrutinib 25 mg QD (Period 1 and Period 2)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
0
52
2
52
19
52
EG003
Evobrutinib 75 mg QD (Period 1 and Period 2)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
0
53
2
53
19
53
EG004
Evobrutinib 75 mg BID (Period 1 and Period 2)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
0
54
4
54
20
54
EG005
Tecfidera (Period 1 and Period 2)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period.
0
54
2
54
30
54
EG006
Placebo + Evobrutinib 25 mg QD (Period 3)
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 mg orally, QD from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
0
39
7
39
30
39
EG007
Evobrutinib 25 mg QD (Period 3)
Participants received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
1
39
12
39
26
39
EG008
Evobrutinib 75 mg QD (Period 3)
Participants received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
0
42
8
42
34
42
EG009
Evobrutinib 75 mg BID (Period 3)
Participants received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
1
44
5
44
31
44
EG010
Tecfidera (Period 3)
Participants received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
1
49
10
49
26
49
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Hepatitis toxic
Hepatobiliary disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG0030 affected53 at risk
EG0041 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
Lyme disease
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Overdose
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG003
Road traffic accident
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Transaminases increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Gastric cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Epilepsy
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Restless legs syndrome
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Abortion spontaneous
Pregnancy, puerperium and perinatal conditions
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pneumonia
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Lung neoplasm
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Peripheral embolism
Vascular disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Microcytic anaemia
Blood and lymphatic system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Myocardial ischaemia
Cardiac disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Sinus tachycardia
Cardiac disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Supraventricular tachycardia
Cardiac disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Keratoconus
Eye disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pyrexia
General disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cholelithiasis
Hepatobiliary disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Hepatitis
Hepatobiliary disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Anaphylactic shock
Immune system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
COVID-19 pneumonia
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Appendicitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Breast abscess
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
COVID-19
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cervicitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Endometritis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Erysipelas
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Escherichia sepsis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Gastroenteritis norovirus
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pulmonary tuberculosis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pyelonephritis acute
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Serratia infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Tonsillitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Femoral neck fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Femur fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Fibula fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Head injury
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Lower limb fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Lumbar vertebral fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Post procedural complication
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Rib fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Sternal fracture
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Lipase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Haemochromatosis
Metabolism and nutrition disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Osteonecrosis
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Fracture pain
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Osteoarthritis
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Ovarian germ cell teratoma benign
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Papilloma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Small cell lung cancer
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cerebellar ischaemia
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cerebral venous sinus thrombosis
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Headache
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Ischaemic stroke
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Multiple sclerosis pseudo relapse
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vertebrobasilar artery dissection
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vertigo CNS origin
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pregnancy
Pregnancy, puerperium and perinatal conditions
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Confusional state
Psychiatric disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Mood disorder due to a general medical condition
Psychiatric disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Bladder hypertrophy
Renal and urinary disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Tubulointerstitial nephritis
Renal and urinary disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cervical dysplasia
Reproductive system and breast disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Heavy menstrual bleeding
Reproductive system and breast disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Uterine cervix stenosis
Reproductive system and breast disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Nasal polyps
Respiratory, thoracic and mediastinal disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Blood pressure fluctuation
Vascular disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Nausea
Gastrointestinal disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0022 affected52 at risk
EG0030 affected53 at risk
EG0041 affected54 at risk
EG0053 affected54 at risk
EG0063 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0103 affected49 at risk
Diarrhoea
Gastrointestinal disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG003
Nasopharyngitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0005 affected54 at risk
EG0011 affected49 at risk
EG0029 affected52 at risk
EG003
Upper respiratory tract infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG003
Alanine aminotransferase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0003 affected54 at risk
EG0011 affected49 at risk
EG0023 affected52 at risk
EG003
Lipase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0002 affected54 at risk
EG0013 affected49 at risk
EG0022 affected52 at risk
EG003
Aspartate aminotransferase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG003
Blood creatinine increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Gamma-glutamyltransferase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0021 affected52 at risk
EG003
Lymphocyte count decreased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
White blood cell count decreased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0001 affected54 at risk
EG0010 affected49 at risk
EG0022 affected52 at risk
EG003
Headache
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0002 affected54 at risk
EG0010 affected49 at risk
EG0023 affected52 at risk
EG003
Erythema
Skin and subcutaneous tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Flushing
Vascular disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Amylase increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0003 affected54 at risk
EG0013 affected49 at risk
EG0020 affected52 at risk
EG003
Urinary tract infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0003 affected54 at risk
EG0010 affected49 at risk
EG0022 affected52 at risk
EG003
Cystitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0013 affected49 at risk
EG0021 affected52 at risk
EG003
Microcytic anaemia
Blood and lymphatic system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vertigo
Ear and labyrinth disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vomiting
Gastrointestinal disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Asthenia
General disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vaccination site pain
General disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
COVID-19
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pharyngitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Respiratory tract infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Laryngitis
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Vulvovaginal mycotic infection
Infections and infestations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Immunisation reaction
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Fall
Injury, poisoning and procedural complications
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Blood bilirubin increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Weight increased
Investigations
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Hypercholesterolaemia
Metabolism and nutrition disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Uterine leiomyoma
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Hypoaesthesia
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Sciatica
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Balance disorder
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Muscle spasticity
Nervous system disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Insomnia
Psychiatric disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Depressed mood
Psychiatric disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Menstruation irregular
Reproductive system and breast disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Cough
Respiratory, thoracic and mediastinal disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Rash
Skin and subcutaneous tissue disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Hypertension
Vascular disorders
MedDRA v21.0,26.1
Non-systematic Assessment
EG0000 affected54 at risk
EG0010 affected49 at risk
EG0020 affected52 at risk
EG003
Reported p values are not adjusted for multiple testing.
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG0000.37(0.17 to 0.70)
OG0010.57(0.30 to 0.97)
OG0020.13(0.03 to 0.38)
OG0030.08(0.01 to 0.30)
OG0040.20(0.06 to 0.47)
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
OG001
Negative Binomial model
0.2692
Qualified relapse rate ratio
1.66
2-Sided
95
0.67
4.09
Superiority
OG000
OG002
Negative Binomial model
0.0896
Qualified relapse rate ratio
0.31
2-Sided
95
0.08
1.20
Superiority
OG000
OG003
Negative Binomial model
0.0633
Qualified relapse rate ratio
0.23
2-Sided
95
0.05
1.09
Superiority
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG00077.4(63.8 to 87.7)
OG00174.0(59.7 to 85.4)
OG00288.2(76.1 to 95.6)
OG00386.8(74.7 to 94.5)
OG00488.9(77.4 to 95.8)
Group IDs
Group Description
Statistical Method
Statistical Comment
P-Value
P-Value Comment
Parameter Type
Parameter Value
Dispersion Type
Dispersion Value
Confidence Interval Sides
Confidence Interval %
CI Lower Limit
CI Upper Limit
CI Lower Limit Comment
CI Upper Limit Comment
Estimate Comment
Tested Non-Inferiority
Non-Inferiority Type
Non-Inferiority Comment
Other Analysis Description
OG000
OG001
Logistic model
0.5609
Odds Ratio (OR)
0.75
2-Sided
95
0.29
1.95
Superiority
OG000
OG002
Logistic model
0.0689
Odds Ratio (OR)
2.79
2-Sided
95
0.92
8.41
Superiority
OG000
OG003
Logistic model
0.1767
Odds Ratio (OR)
2.08
2-Sided
95
0.72
5.99
Superiority
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG000-0.03± 0.301
OG0010.02± 0.622
OG002-0.14± 0.664
OG0030.04± 0.216
OG0040.02± 0.274
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
OG001
Wilcoxon rank-sum test
0.4070
Hodges-Lehmann estimate
0.00
2-Sided
95
0.00
0.00
Superiority
OG000
OG002
Wilcoxon rank-sum test
0.5829
Hodges-Lehmann estimate
0.00
2-Sided
95
0.00
0.00
Superiority
OG000
OG003
Wilcoxon rank-sum test
0.2732
Hodges-Lehmann estimate
0.00
2-Sided
95
0.00
0.00
Superiority
Participants who received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1 received Evobrutinib 25 milligram (mg) orally, once daily (QD) in blinded extension (BE) period from week 25 to week 48.
OG002
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG005
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00054
OG00149
OG00252
OG00353
OG00454
OG00554
Title
Denominators
Categories
TEAEs
Title
Measurements
OG00024
OG00119
OG00228
OG00335
OG00434
OG00535
Serious TEAEs
Title
Measurements
OG0002
OG0010
OG0022
OG003
TEAEs Leading to Death
Title
Measurements
OG0000
OG0010
OG0020
OG003
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG005
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00054
OG00149
OG00252
OG00353
OG00454
OG00554
Title
Denominators
Categories
Vital Sign Abnormalities
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
OG0050
ECG Abnormalities
Title
Measurements
OG0000
OG0010
OG0020
OG003
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG005
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00054
OG00149
OG00252
OG00353
OG00454
OG00554
Title
Denominators
Categories
Grade >= 3 hematology values
Title
Measurements
OG0000
OG0012
OG0020
OG0031
OG0040
OG0051
Grade >= 3 biochemistry values
Title
Measurements
OG0002
OG0018
OG0026
OG003
Grade >= 3 or value >= 2 ULN or ++ Increasing urinalysis values
Title
Measurements
OG0000
OG0012
OG0021
OG003
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00054
OG00152
OG00253
OG00354
OG00454
Title
Denominators
Categories
Ig A, Day 1
ParticipantsOG00054
ParticipantsOG00151
ParticipantsOG00253
ParticipantsOG00354
ParticipantsOG00454
Title
Measurements
OG0001.99± 0.777
OG0011.89± 0.764
OG0021.90± 0.722
OG003
Ig A, Week 4
ParticipantsOG00054
ParticipantsOG00152
ParticipantsOG00253
ParticipantsOG00354
Ig A, Week 16
ParticipantsOG00053
ParticipantsOG00150
ParticipantsOG00249
ParticipantsOG00353
Ig A, Week 24
ParticipantsOG00050
ParticipantsOG00147
ParticipantsOG00249
ParticipantsOG00348
Ig G, Day 1
ParticipantsOG00054
ParticipantsOG00151
ParticipantsOG00253
ParticipantsOG00354
Ig G, Week 4
ParticipantsOG00054
ParticipantsOG00152
ParticipantsOG00253
ParticipantsOG00354
Ig G, Week 16
ParticipantsOG00053
ParticipantsOG00150
ParticipantsOG00249
ParticipantsOG00353
Ig G, Week 24
ParticipantsOG00050
ParticipantsOG00147
ParticipantsOG00249
ParticipantsOG00348
Ig M, Day 1
ParticipantsOG00054
ParticipantsOG00151
ParticipantsOG00253
ParticipantsOG00354
Ig M, Week 4
ParticipantsOG00054
ParticipantsOG00151
ParticipantsOG00253
ParticipantsOG00354
Ig M, Week 16
ParticipantsOG00053
ParticipantsOG00150
ParticipantsOG00249
ParticipantsOG00353
Ig M, Week 24
ParticipantsOG00049
ParticipantsOG00147
ParticipantsOG00249
ParticipantsOG00348
OG003
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00050
OG00151
OG00254
OG00352
Title
Denominators
Categories
IgA
Title
Measurements
OG0002.13± 0.807
OG0012.18± 0.790
OG0022.23± 0.838
OG0032.06± 0.695
IgG
Title
Measurements
OG0009.53± 2.070
OG0019.74± 1.902
OG0029.38± 2.189
OG003
IgM
Title
Measurements
OG0001.08± 0.557
OG0011.13± 0.639
OG0021.10± 0.692
OG003
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00054
OG00150
OG00253
OG00354
OG00454
Title
Denominators
Categories
Ig A, Week 4
ParticipantsOG00054
ParticipantsOG00150
ParticipantsOG00253
ParticipantsOG00354
ParticipantsOG00454
Title
Measurements
OG000-0.02± 0.201
OG0010.02± 0.165
OG0020.04± 0.169
OG003
Ig A, Week 16
ParticipantsOG00051
ParticipantsOG00148
ParticipantsOG00249
ParticipantsOG00353
Ig A, Week 24
ParticipantsOG00049
ParticipantsOG00144
ParticipantsOG00248
ParticipantsOG00348
Ig G, Week 4
ParticipantsOG00054
ParticipantsOG00150
ParticipantsOG00253
ParticipantsOG00354
Ig G, Week 16
ParticipantsOG00053
ParticipantsOG00148
ParticipantsOG00249
ParticipantsOG00353
Ig G, Week 24
ParticipantsOG00050
ParticipantsOG00145
ParticipantsOG00249
ParticipantsOG00348
Ig M, Week 4
ParticipantsOG00054
ParticipantsOG00150
ParticipantsOG00253
ParticipantsOG00354
Ig M, Week 16
ParticipantsOG00053
ParticipantsOG00148
ParticipantsOG00249
ParticipantsOG00353
Ig M, Week 24
ParticipantsOG00050
ParticipantsOG00145
ParticipantsOG00249
ParticipantsOG00348
OG003
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00048
OG00151
OG00254
OG00352
Title
Denominators
Categories
IgA
Title
Measurements
OG0000.26± 0.248
OG0010.28± 0.275
OG0020.36± 0.320
OG0030.03± 0.316
IgG
Title
Measurements
OG0000.11± 1.024
OG001-0.08± 0.940
OG002-0.24± 0.883
OG003
IgM
Title
Measurements
OG000-0.18± 0.211
OG001-0.27± 0.287
OG002-0.23± 0.218
OG003
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00052
OG00152
OG00253
OG00353
OG00452
Title
Denominators
Categories
Day 1
ParticipantsOG00052
ParticipantsOG00152
ParticipantsOG00249
ParticipantsOG00351
ParticipantsOG00448
Title
Measurements
OG000242± 134.2
OG001208± 117.5
OG002247± 131.8
OG003
Week 4
ParticipantsOG00052
ParticipantsOG00150
ParticipantsOG00253
ParticipantsOG00353
Week 24
ParticipantsOG00049
ParticipantsOG00144
ParticipantsOG00249
ParticipantsOG00347
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00049
OG00151
OG00254
OG00347
Title
Denominators
Categories
Week 48
ParticipantsOG00049
ParticipantsOG00151
ParticipantsOG00254
ParticipantsOG00347
Title
Measurements
OG000203± 111.9
OG001222± 148.8
OG002187± 87.1
OG003
Week 52
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0028
ParticipantsOG0032
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00052
OG00150
OG00253
OG00353
OG00452
Title
Denominators
Categories
Week 4
ParticipantsOG00052
ParticipantsOG00150
ParticipantsOG00253
ParticipantsOG00353
ParticipantsOG00452
Title
Measurements
OG000-5± 94.5
OG0019± 112.2
OG00231± 114.2
OG003
Week 24
ParticipantsOG00049
ParticipantsOG00144
ParticipantsOG00249
ParticipantsOG00347
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00049
OG00151
OG00254
OG00347
Title
Denominators
Categories
Week 48
ParticipantsOG00049
ParticipantsOG00151
ParticipantsOG00254
ParticipantsOG00347
Title
Measurements
OG000-5± 116.1
OG001-30± 148.2
OG002-32± 97.9
OG003
Week 52
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0028
ParticipantsOG0032
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG0003.08± 4.371
OG0013.44± 6.846
OG0021.20± 3.499
OG0030.98± 3.273
OG0043.24± 15.320
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
OG001
Negative Binomial
0.3676
Lesion rate ratio
1.36
2-Sided
95
0.70
2.65
Superiority
OG000
OG002
Negative Binomial
0.0005
Lesion rate ratio
0.27
2-Sided
95
0.13
0.57
Superiority
OG000
OG003
Negative Binomial
0.0157
Lesion rate ratio
0.41
2-Sided
95
0.20
0.85
Superiority
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG0001.02± 1.439
OG0011.31± 3.130
OG0020.42± 1.173
OG0030.34± 0.960
OG0041.45± 7.293
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
OG001
Wilcoxon rank-sum test
0.9731
Hodges-Lehmann estimate
0.00
2-Sided
95
-0.25
0.25
Superiority
OG000
OG002
Wilcoxon rank-sum test
0.0017
Hodges-Lehmann estimate
-0.25
2-Sided
95
-0.50
0.00
Superiority
OG000
OG003
Wilcoxon rank-sum test
< 0.0001
Hodges-Lehmann estimate
-0.50
2-Sided
95
-0.75
-0.25
Superiority
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG0005.96± 6.994
OG0016.52± 11.569
OG0023.41± 10.752
OG0032.19± 4.719
OG0045.35± 16.667
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
OG001
Negative Binomial
0.4807
Lesion Rate ratio
1.29
2-Sided
95
0.63
2.65
Superiority
OG000
OG002
Negative Binomial
0.0620
Lesion Rate ratio
0.50
2-Sided
95
0.24
1.04
Superiority
OG000
OG003
Negative Binomial
0.0189
Lesion Rate ratio
0.42
2-Sided
95
0.20
0.87
Superiority
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00146
OG00248
OG00346
OG00450
Title
Denominators
Categories
Title
Measurements
OG0000.42± 1.009
OG0010.93± 1.853
OG002-0.01± 0.562
OG0030.09± 0.463
OG0040.47± 2.964
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
OG001
Mixed Effect Model for Repeat Measures
0.8776
Difference in least squares means
0.02
2-Sided
95
-0.24
0.28
Difference in least squares means of change from baseline in cube root of volume measured in centimeter.
Superiority
OG000
OG002
Mixed Effect Model for Repeat Measures
0.0019
Difference in least squares means
-0.41
2-Sided
95
-0.66
-0.15
Difference in least squares means of change from baseline in cube root of volume measured in centimeter.
Superiority
OG000
OG003
Mixed Effect Model for Repeat Measures
0.0063
Difference in least squares means
-0.36
2-Sided
95
-0.62
-0.10
Difference in least squares means of change from baseline in cube root of volume measured in centimeter.
Superiority
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG000-0.023± 0.2220
OG0010.057± 0.3479
OG002-0.111± 0.5416
OG003-0.051± 0.1032
OG004-0.050± 0.4771
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
OG001
Wilcoxon rank-sum test
0.9315
Hodges-Lehmann estimate
0.00
2-Sided
95
-0.004
0.009
Superiority
OG000
OG002
Wilcoxon rank-sum test
0.0008
Hodges-Lehmann estimate
-0.014
2-Sided
95
-0.050
0.000
Superiority
OG000
OG003
Wilcoxon rank-sum test
0.0014
Hodges-Lehmann estimate
-0.018
2-Sided
95
-0.042
0.000
Superiority
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG0001.00± 1.614
OG0011.91± 4.296
OG0020.85± 2.867
OG0030.49± 1.218
OG0040.42± 1.444
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG0000.95± 1.569
OG0011.84± 4.154
OG0020.85± 2.867
OG0030.49± 1.218
OG0040.42± 1.444
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00053
OG00150
OG00251
OG00353
OG00454
Title
Denominators
Categories
Title
Measurements
OG0000.37(0.21 to 0.59)
OG0010.52(0.33 to 0.78)
OG0020.25(0.12 to 0.44)
OG0030.11(0.04 to 0.25)
OG0040.14(0.06 to 0.29)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG00084.1
OG00186.4
OG00278.3
OG00391.1
OG00496.0
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG000-0.05± 0.260
OG001-0.10± 0.351
OG002-0.01± 0.619
OG0030.00± 0.238
OG004-0.10± 0.404
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00042
OG00142
OG00243
OG00343
OG00450
Title
Denominators
Categories
Title
Measurements
OG0003.57± 4.346
OG0015.86± 11.330
OG0023.84± 10.083
OG0031.60± 3.799
OG0041.88± 4.796
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG0000.092± 0.4626
OG0010.088± 0.4006
OG0020.045± 0.2285
OG0030.024± 0.1981
OG004-0.203± 1.1073
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00044
OG00144
OG00246
OG00345
OG00450
Title
Denominators
Categories
Title
Measurements
OG0000.53± 1.360
OG0010.67± 1.865
OG0020.35± 1.083
OG003-0.03± 1.031
OG004-0.57± 2.699
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00034
OG00135
OG00237
OG00344
OG00437
Title
Denominators
Categories
OLE Baseline (BE period Week 48)
ParticipantsOG00034
ParticipantsOG00135
ParticipantsOG00237
ParticipantsOG00344
ParticipantsOG00437
Title
Measurements
OG0000.82± 2.668
OG0011.74± 4.395
OG0021.46± 4.519
OG003
Week 96
ParticipantsOG00031
ParticipantsOG00127
ParticipantsOG00235
ParticipantsOG00336
Week 144
ParticipantsOG00029
ParticipantsOG00127
ParticipantsOG00234
ParticipantsOG00335
Week 192
ParticipantsOG00028
ParticipantsOG00125
ParticipantsOG00232
ParticipantsOG00332
Week 240
ParticipantsOG00025
ParticipantsOG00124
ParticipantsOG00230
ParticipantsOG00330
Week 288
ParticipantsOG00020
ParticipantsOG00117
ParticipantsOG00228
ParticipantsOG00326
Week 336
ParticipantsOG0006
ParticipantsOG0017
ParticipantsOG0026
ParticipantsOG0037
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00138
OG00242
OG00344
OG00448
Title
Denominators
Categories
OLE Baseline (BE period Week 48)
ParticipantsOG00039
ParticipantsOG00138
ParticipantsOG00242
ParticipantsOG00344
ParticipantsOG00448
Title
Measurements
OG0000.29(0.14 to 0.53)
OG0010.18(0.06 to 0.38)
OG0020.14(0.04 to 0.32)
OG003
Week 96
ParticipantsOG00037
ParticipantsOG00136
ParticipantsOG00237
ParticipantsOG00344
Week 144
ParticipantsOG00033
ParticipantsOG00130
ParticipantsOG00237
ParticipantsOG00340
Week 192
ParticipantsOG00031
ParticipantsOG00127
ParticipantsOG00235
ParticipantsOG00335
Week 240
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00234
ParticipantsOG00333
Week 288
ParticipantsOG00025
ParticipantsOG00124
ParticipantsOG00232
ParticipantsOG00332
Week 336
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00226
ParticipantsOG00329
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00138
OG00242
OG00344
OG00448
Title
Denominators
Categories
Title
Measurements
OG00066.7
OG00168.4
OG00271.4
OG00365.9
OG00483.3
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00138
OG00242
OG00344
OG00448
Title
Denominators
Categories
OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00135
ParticipantsOG00228
ParticipantsOG00344
ParticipantsOG00440
Title
Measurements
OG0000.1± 0.39
OG0010.0± 0.69
OG0020.1± 0.46
OG003
Week 96
ParticipantsOG00034
ParticipantsOG00130
ParticipantsOG00235
ParticipantsOG00338
Week 144
ParticipantsOG00031
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
Week 192
ParticipantsOG00028
ParticipantsOG00126
ParticipantsOG00234
ParticipantsOG00333
Week 240
ParticipantsOG00025
ParticipantsOG00125
ParticipantsOG00232
ParticipantsOG00332
Week 288
ParticipantsOG00023
ParticipantsOG00123
ParticipantsOG00229
ParticipantsOG00329
Week 336
ParticipantsOG00011
ParticipantsOG00110
ParticipantsOG00210
ParticipantsOG0037
OG001
Evobrutinib 25 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 25 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG002
Evobrutinib 75 mg QD (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00139
OG00242
OG00344
OG00449
Title
Denominators
Categories
Title
Measurements
OG00035
OG00129
OG00241
OG00340
OG00437
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00139
OG00242
OG00344
OG00449
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00139
OG00242
OG00344
OG00449
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00039
OG00139
OG00242
OG00344
OG00449
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0030
OG0040
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00344
OG00440
Title
Denominators
Categories
Ig A, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
ParticipantsOG00440
Title
Measurements
OG0002.31± 0.966
OG0012.44± 0.897
OG0022.49± 0.953
OG003
Ig A, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
Ig A, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
Ig A, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
IgA, Week 192
ParticipantsOG00029
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
IgA, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
IgA, Week 288
ParticipantsOG00037
ParticipantsOG00120
ParticipantsOG00226
ParticipantsOG00327
Ig G, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
Ig G, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
Ig G, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
Ig G, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
IgG, Week 192
ParticipantsOG00029
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
IgG, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
IgG, Week 288
ParticipantsOG00025
ParticipantsOG00120
ParticipantsOG00226
ParticipantsOG00327
Ig M, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
Ig M, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
Ig M, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
Ig M, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
Ig M, Week 192
ParticipantsOG00028
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
Ig M, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
Ig M, Week 288
ParticipantsOG00025
ParticipantsOG00122
ParticipantsOG00227
ParticipantsOG00328
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg QD orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG003
Evobrutinib 75 mg BID (Period 1, 2 and 3)
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period received Evobrutinib 75 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
OG004
Tecfidera (Period 1, 2 and 3)
Participants received Tecfidera 120 mg twice daily (BID) for first 7 days followed by 240 mg orally, BID up to Week 48 in active treatment period 1 and BE period received Tecfidera 120 mg BID orally from Week 48 of BE period (OLE period Day 1) to Week 336 in OLE period.
Units
Counts
Participants
OG00037
OG00137
OG00237
OG00344
OG00440
Title
Denominators
Categories
Ig A, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
ParticipantsOG00440
Title
Measurements
OG0000.26± 0.237
OG0010.17± 0.333
OG0020.19± 0.283
OG003
Ig A, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
Ig A, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
Ig A, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
IgA, Week 192
ParticipantsOG00029
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
IgA, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
IgA, Week 288
ParticipantsOG00025
ParticipantsOG00120
ParticipantsOG00226
ParticipantsOG00327
Ig G, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
Ig G, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
Ig G, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
Ig G, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
IgG, Week 192
ParticipantsOG00029
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
IgG, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
IgG, Week 288
ParticipantsOG00025
ParticipantsOG00120
ParticipantsOG00226
ParticipantsOG00327
Ig M, OLE Baseline (BE period Week 48)
ParticipantsOG00037
ParticipantsOG00137
ParticipantsOG00237
ParticipantsOG00344
IgM, Week 72
ParticipantsOG00034
ParticipantsOG00132
ParticipantsOG00235
ParticipantsOG00343
IgM, Week 96
ParticipantsOG00032
ParticipantsOG00130
ParticipantsOG00236
ParticipantsOG00339
IgM, Week 144
ParticipantsOG00030
ParticipantsOG00127
ParticipantsOG00236
ParticipantsOG00335
IgM, Week 192
ParticipantsOG00028
ParticipantsOG00126
ParticipantsOG00233
ParticipantsOG00332
IgM, Week 240
ParticipantsOG00024
ParticipantsOG00122
ParticipantsOG00233
ParticipantsOG00328
IgM, Week 288
ParticipantsOG00025
ParticipantsOG00122
ParticipantsOG00227
ParticipantsOG00328
0 affected
53 at risk
EG0040 affected54 at risk
EG0051 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
1 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0041 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0051 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0041 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0041 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
1 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0072 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0102 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0082 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0054 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0103 affected49 at risk
3 affected
53 at risk
EG0047 affected54 at risk
EG0052 affected54 at risk
EG0067 affected39 at risk
EG0077 affected39 at risk
EG0088 affected42 at risk
EG0099 affected44 at risk
EG0104 affected49 at risk
1 affected
53 at risk
EG0041 affected54 at risk
EG0053 affected54 at risk
EG0065 affected39 at risk
EG0072 affected39 at risk
EG0086 affected42 at risk
EG0094 affected44 at risk
EG0103 affected49 at risk
6 affected
53 at risk
EG0045 affected54 at risk
EG0053 affected54 at risk
EG0061 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0105 affected49 at risk
5 affected
53 at risk
EG0045 affected54 at risk
EG0053 affected54 at risk
EG0065 affected39 at risk
EG0076 affected39 at risk
EG0086 affected42 at risk
EG0098 affected44 at risk
EG0105 affected49 at risk
2 affected
53 at risk
EG0044 affected54 at risk
EG0052 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
3 affected
53 at risk
EG0043 affected54 at risk
EG0051 affected54 at risk
EG0062 affected39 at risk
EG0071 affected39 at risk
EG0082 affected42 at risk
EG0093 affected44 at risk
EG0101 affected49 at risk
1 affected
53 at risk
EG0043 affected54 at risk
EG0051 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0103 affected49 at risk
0 affected
53 at risk
EG0041 affected54 at risk
EG0055 affected54 at risk
EG0061 affected39 at risk
EG0072 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0102 affected49 at risk
0 affected
53 at risk
EG0041 affected54 at risk
EG0053 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
3 affected
53 at risk
EG0040 affected54 at risk
EG0054 affected54 at risk
EG0065 affected39 at risk
EG0073 affected39 at risk
EG0081 affected42 at risk
EG0092 affected44 at risk
EG0102 affected49 at risk
2 affected
53 at risk
EG0041 affected54 at risk
EG0051 affected54 at risk
EG0063 affected39 at risk
EG0072 affected39 at risk
EG0085 affected42 at risk
EG0096 affected44 at risk
EG0104 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0057 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG00512 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0072 affected39 at risk
EG0081 affected42 at risk
EG0091 affected44 at risk
EG0101 affected49 at risk
1 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0067 affected39 at risk
EG0075 affected39 at risk
EG0087 affected42 at risk
EG0095 affected44 at risk
EG0103 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0074 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0071 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0103 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0072 affected39 at risk
EG0083 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0082 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0066 affected39 at risk
EG0078 affected39 at risk
EG0083 affected42 at risk
EG0096 affected44 at risk
EG0107 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0071 affected39 at risk
EG0083 affected42 at risk
EG0092 affected44 at risk
EG0102 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0071 affected39 at risk
EG0084 affected42 at risk
EG0091 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0072 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0072 affected39 at risk
EG0081 affected42 at risk
EG0091 affected44 at risk
EG0103 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0071 affected39 at risk
EG0080 affected42 at risk
EG0094 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0104 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0071 affected39 at risk
EG0081 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0075 affected39 at risk
EG0089 affected42 at risk
EG0093 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0074 affected39 at risk
EG0083 affected42 at risk
EG0091 affected44 at risk
EG0103 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0072 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0071 affected39 at risk
EG0081 affected42 at risk
EG0092 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0073 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0072 affected39 at risk
EG0080 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0070 affected39 at risk
EG0083 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0082 affected42 at risk
EG0090 affected44 at risk
EG0102 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0070 affected39 at risk
EG0083 affected42 at risk
EG0091 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0080 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0061 affected39 at risk
EG0071 affected39 at risk
EG0083 affected42 at risk
EG0092 affected44 at risk
EG0101 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0060 affected39 at risk
EG0072 affected39 at risk
EG0083 affected42 at risk
EG0090 affected44 at risk
EG0100 affected49 at risk
0 affected
53 at risk
EG0040 affected54 at risk
EG0050 affected54 at risk
EG0062 affected39 at risk
EG0070 affected39 at risk
EG0082 affected42 at risk
EG0092 affected44 at risk
EG0102 affected49 at risk
2
OG0044
OG0052
0
OG0040
OG0050
0
OG0040
OG0050
9
OG00416
OG0059
2
OG0042
OG0056
1.87
± 0.675
OG0042.03± 0.763
Participants
OG004
54
Title
Measurements
OG0001.98± 0.777
OG0011.92± 0.770
OG0021.93± 0.762
OG0031.94± 0.748
OG0041.90± 0.699
ParticipantsOG00452
Title
Measurements
OG0002.07± 0.824
OG0012.10± 0.813
OG0022.13± 0.832
OG0032.08± 0.753
OG0042.03± 0.752
ParticipantsOG00452
Title
Measurements
OG0001.99± 0.807
OG0012.12± 0.833
OG0022.09± 0.838
OG0032.09± 0.793
OG0041.97± 0.757
Participants
OG004
54
Title
Measurements
OG0009.61± 1.897
OG0019.43± 2.126
OG0029.81± 1.841
OG0039.62± 1.960
OG0049.47± 1.839
Participants
OG004
54
Title
Measurements
OG0009.64± 2.094
OG0019.34± 1.972
OG0029.79± 1.910
OG0039.64± 1.987
OG0049.05± 1.922
ParticipantsOG00452
Title
Measurements
OG0009.68± 2.085
OG0019.41± 2.077
OG0029.70± 1.991
OG0039.56± 2.129
OG0049.58± 1.850
ParticipantsOG00452
Title
Measurements
OG0009.66± 2.081
OG0019.46± 2.123
OG0029.62± 2.048
OG0039.36± 1.988
OG0049.27± 1.866
Participants
OG004
54
Title
Measurements
OG0001.42± 0.692
OG0011.27± 0.542
OG0021.44± 0.716
OG0031.33± 0.684
OG0041.27± 0.589
Participants
OG004
54
Title
Measurements
OG0001.40± 0.668
OG0011.21± 0.526
OG0021.32± 0.654
OG0031.28± 0.656
OG0041.23± 0.603
ParticipantsOG00452
Title
Measurements
OG0001.43± 0.703
OG0011.13± 0.558
OG0021.24± 0.639
OG0031.20± 0.689
OG0041.28± 0.678
ParticipantsOG00452
Title
Measurements
OG0001.44± 0.748
OG0011.03± 0.499
OG0021.20± 0.672
OG0031.08± 0.494
OG0041.29± 0.667
9.60
± 1.968
1.28
± 0.635
0.07
± 0.195
OG004-0.13± 0.238
ParticipantsOG00452
Title
Measurements
OG0000.10± 0.188
OG0010.18± 0.245
OG0020.21± 0.313
OG0030.22± 0.209
OG004-0.02± 0.274
ParticipantsOG00452
Title
Measurements
OG0000.06± 0.250
OG0010.21± 0.283
OG0020.18± 0.416
OG0030.22± 0.229
OG004-0.06± 0.207
Participants
OG004
54
Title
Measurements
OG0000.02± 0.758
OG001-0.10± 0.697
OG002-0.02± 0.688
OG0030.02± 0.581
OG004-0.42± 0.926
ParticipantsOG00452
Title
Measurements
OG0000.04± 0.747
OG001-0.07± 0.964
OG002-0.10± 1.068
OG003-0.05± 0.710
OG0040.07± 0.961
ParticipantsOG00452
Title
Measurements
OG0000.06± 0.682
OG0010.00± 1.228
OG002-0.15± 1.058
OG003-0.28± 0.774
OG004-0.23± 0.882
Participants
OG004
54
Title
Measurements
OG000-0.01± 0.210
OG001-0.06± 0.100
OG002-0.12± 0.233
OG003-0.05± 0.133
OG004-0.04± 0.132
ParticipantsOG00452
Title
Measurements
OG0000.02± 0.177
OG001-0.12± 0.184
OG002-0.18± 0.244
OG003-0.14± 0.189
OG004-0.00± 0.184
ParticipantsOG00452
Title
Measurements
OG0000.04± 0.163
OG001-0.14± 0.286
OG002-0.20± 0.289
OG003-0.21± 0.167
OG004-0.00± 0.186
0.10
± 1.244
-0.01
± 0.198
219
± 113.7
OG004210± 97.4
Participants
OG004
52
Title
Measurements
OG000243± 130.8
OG001220± 92.7
OG002277± 156.2
OG003270± 143.2
OG004201± 114.3
Participants
OG004
52
Title
Measurements
OG000264± 154.9
OG001230± 119.7
OG002235± 115.3
OG003214± 105.0
OG004180± 114.3
181
± 109.8
Title
Measurements
OG000227± 93.7
OG001206± 140.3
OG002154± 73.6
OG003135± 29.0
50
± 86.7
OG004-3± 111.0
Participants
OG004
52
Title
Measurements
OG0007± 135.8
OG00113± 98.2
OG002-15± 128.5
OG003-9± 85.1
OG004-26± 113.9
-15
± 105.7
Title
Measurements
OG000-28± 209.8
OG001-25± 65.5
OG002-81± 119.0
OG00315± 22.6
1.16
± 3.050
OG0042.03± 11.829
Participants
OG004
36
Title
Measurements
OG0000.13± 0.341
OG0010.63± 1.822
OG0020.49± 1.121
OG0030.69± 1.411
OG0040.67± 2.255
Participants
OG004
31
Title
Measurements
OG0000.76± 2.294
OG0010.41± 1.217
OG0020.82± 3.512
OG0030.54± 1.146
OG0041.29± 5.940
Participants
OG004
26
Title
Measurements
OG0001.00± 3.367
OG0010.64± 1.890
OG0020.81± 2.206
OG0030.84± 1.798
OG0040.96± 3.130
Participants
OG004
26
Title
Measurements
OG0001.68± 5.800
OG0010.63± 1.996
OG0020.37± 1.189
OG0030.77± 2.417
OG0040.88± 3.204
Participants
OG004
23
Title
Measurements
OG0000.35± 0.671
OG0010.35± 0.786
OG0020.32± 1.090
OG0031.04± 2.946
OG0040.35± 1.265
Participants
OG004
15
Title
Measurements
OG0000.83± 1.602
OG0013.00± 5.745
OG0021.17± 2.858
OG0030.29± 0.756
OG0045.60± 18.310
0.17
(0.07 to 0.36)
OG0040.12(0.04 to 0.28)
Participants
OG004
40
Title
Measurements
OG0000.16(0.05 to 0.37)
OG0010.13(0.04 to 0.34)
OG0020.09(0.02 to 0.26)
OG0030.08(0.02 to 0.22)
OG0040.03(0.00 to 0.16)
Participants
OG004
36
Title
Measurements
OG0000.07(0.01 to 0.25)
OG0010.11(0.02 to 0.33)
OG0020.03(0.00 to 0.17)
OG0030.15(0.05 to 0.34)
OG0040.16(0.05 to 0.37)
Participants
OG004
33
Title
Measurements
OG0000.04(0.00 to 0.20)
OG0010.08(0.01 to 0.29)
OG0020.22(0.09 to 0.45)
OG0030.16(0.05 to 0.38)
OG0040.04(0.00 to 0.20)
Participants
OG004
30
Title
Measurements
OG0000.16(0.04 to 0.41)
OG0010.04(0.00 to 0.23)
OG0020.10(0.02 to 0.28)
OG0030.13(0.04 to 0.34)
OG0040.00(NA to 0.15)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
Participants
OG004
26
Title
Measurements
OG0000.13(0.13 to 0.38)
OG0010.05(0.00 to 0.25)
OG0020.07(0.01 to 0.25)
OG0030.00(NA to 0.13)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
OG0040.04(0.00 to 0.24)
Participants
OG004
7
Title
Measurements
OG0000.00(NA to 1.75)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
OG0010.00(NA to 1.55)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
OG0020.31(0.01 to 1.70)
OG0030.00(NA to 1.27)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.
OG0040.00(NA to 7.97)Based on pre-specified criteria, when the number of qualified relapses is zero, the lower limit of 95% confidence interval could not be calculated.