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A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis

Primary Purpose

Relapsing-remitting Multiple Sclerosis

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Evobrutinib
Evobrutinib
Evobrutinib
Placebo
Tecfidera
Evobrutinib
Sponsored by
EMD Serono Research & Development Institute, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsing-remitting Multiple Sclerosis focused on measuring M2951, Relapsing Multiple Sclerosis, Bruton's Tyrosine Kinase inhibitor

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site 1
  • Research Site 2
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Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Experimental

Experimental

Experimental

Experimental

Active Comparator

Placebo Comparator

Arm Label

Placebo then Evobrutinib 25 mg QD

Evobrutinib 25 mg QD

Evobrutinib 75 mg QD

Evobrutinib 75 mg BID

Tecfidera

Placebo

Arm Description

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.

Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.

Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.

Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.

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.

Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
Absolute Concentrations serum levels of IgG, IgA, IgM were to be assessed.
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Change in the serum levels of IgG, IgA, IgM were assessed.
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
Change in the serum levels of IgG, IgA, IgM were to be assessed.
Absolute Numbers of B Cells (Active Treatment Period)
Absolute Numbers of B Cells are reported.
Absolute Numbers of B Cells (Blinded Extension Period)
Absolute Numbers of B Cells to be reported.
Change From Baseline in Absolute B Cells (Active Treatment Period)
Change from baseline in absolute B cells are reported.
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Change from baseline in absolute B cells to be reported.
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.
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.
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.
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.
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.
Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
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.
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.
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.
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).
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.
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.
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.

Full Information

First Posted
November 23, 2016
Last Updated
September 28, 2023
Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT02975349
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.
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 7, 2017 (Actual)
Primary Completion Date
January 24, 2018 (Actual)
Study Completion Date
February 15, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsing-remitting Multiple Sclerosis
Keywords
M2951, Relapsing Multiple Sclerosis, Bruton's Tyrosine Kinase inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
InvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
267 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo then Evobrutinib 25 mg QD
Arm Type
Experimental
Arm Description
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.
Arm Title
Evobrutinib 25 mg QD
Arm Type
Experimental
Arm Description
Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
Arm Title
Evobrutinib 75 mg QD
Arm Type
Experimental
Arm Description
Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
Arm Title
Evobrutinib 75 mg BID
Arm Type
Experimental
Arm Description
Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
Arm Title
Tecfidera
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
Intervention Type
Drug
Intervention Name(s)
Evobrutinib
Other Intervention Name(s)
M2951
Intervention Description
Participants received Evobrutinib 75 milligrams (mg) orally, twice daily (BID) up to Week 48
Intervention Type
Drug
Intervention Name(s)
Evobrutinib
Other Intervention Name(s)
M2951
Intervention Description
Participants received Evobrutinib 25 mg orally, once daily (QD) up to Week 48
Intervention Type
Drug
Intervention Name(s)
Evobrutinib
Other Intervention Name(s)
M2951
Intervention Description
Participants received Evobrutinib 75 mg orally, QD up to Week 48
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo were administered for 24 weeks
Intervention Type
Drug
Intervention Name(s)
Tecfidera
Intervention Description
Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (48 weeks).
Intervention Type
Drug
Intervention Name(s)
Evobrutinib
Other Intervention Name(s)
M2951
Intervention Description
Following Placebo for 24 weeks, participants received Evobrutinib 25 milligram (mg) orally, once daily (QD) from Week 24 to 48 weeks.
Primary Outcome Measure Information:
Title
Total Number of Gadolinium-Enhancing T1 Lesions
Description
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.
Time Frame
Week 12 to Week 24
Secondary Outcome Measure Information:
Title
Annualized Relapse Rate (ARR) at Week 24
Description
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.
Time Frame
Week 24
Title
Qualified Relapse-Free Status at Week 24
Description
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.
Time Frame
Week 24
Title
Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
Description
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.
Time Frame
Baseline up to Safety Follow-up (Week 52)
Title
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
Description
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.
Time Frame
Baseline up to Safety Follow-up (Week 52)
Title
Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
Description
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.
Time Frame
Baseline up to Safety Follow-up (Week 52)
Title
Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
Description
Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
Time Frame
Baseline (Day 1), Weeks 4, 16, and 24
Title
Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
Description
Absolute Concentrations serum levels of IgG, IgA, IgM were to be assessed.
Time Frame
Weeks 48
Title
Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
Description
Change in the serum levels of IgG, IgA, IgM were assessed.
Time Frame
Baseline (Day 1), Weeks 4, 16, and 24
Title
Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
Description
Change in the serum levels of IgG, IgA, IgM were to be assessed.
Time Frame
Baseline (Day 1), Week 48
Title
Absolute Numbers of B Cells (Active Treatment Period)
Description
Absolute Numbers of B Cells are reported.
Time Frame
Baseline (Day 1), Weeks 4, and 24
Title
Absolute Numbers of B Cells (Blinded Extension Period)
Description
Absolute Numbers of B Cells to be reported.
Time Frame
Weeks 48 and 52
Title
Change From Baseline in Absolute B Cells (Active Treatment Period)
Description
Change from baseline in absolute B cells are reported.
Time Frame
Baseline (Day 1), Weeks 4, and 24
Title
Change From Baseline in Absolute B Cells (Blinded Extension Period)
Description
Change from baseline in absolute B cells to be reported.
Time Frame
Weeks 48 and 52
Title
Total Number of New Gadolinium-positive (Gd+) T1 Lesions
Description
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.
Time Frame
Week 12 to 24
Title
Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
Description
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.
Time Frame
Week 12 to Week 24
Title
Total Number of New or Enlarging T2 Lesions
Description
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.
Time Frame
Week 12 to Week 24
Title
Change From Baseline in Volume of T2 Lesions at Week 24
Description
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.
Time Frame
Baseline, Week 24
Title
Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
Description
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.
Time Frame
Baseline, Week 24
Title
Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Description
Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame
Week 48
Title
Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
Description
Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame
Week 48
Title
Annualized Relapse Rate (ARR)
Description
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.
Time Frame
Week 0 to Week 48
Title
Qualified Relapse-free Status
Description
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.
Time Frame
Week 25 to Week 48
Title
Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
Description
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).
Time Frame
Week 24, Week 48
Title
Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
Description
Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame
Week 24 to Week 48
Title
Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
Description
Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame
Week 24, Week 48
Title
Change From Week 24 in Volume of T2 Lesions at Week 48
Description
Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.
Time Frame
Week 24, Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Blagoevgrad
ZIP/Postal Code
2700
Country
Bulgaria
Facility Name
Research Site
City
Dupnitsa
ZIP/Postal Code
2600
Country
Bulgaria
Facility Name
Research Site 1
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
Research Site 2
City
Pleven
ZIP/Postal Code
5800
Country
Bulgaria
Facility Name
Research Site
City
Ruse
ZIP/Postal Code
7002
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1142
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1309
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1336
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1407
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1606
Country
Bulgaria
Facility Name
Research Site
City
Sofia
ZIP/Postal Code
1797
Country
Bulgaria
Facility Name
Research Site
City
Brno
ZIP/Postal Code
656 91
Country
Czechia
Facility Name
Research Site
City
Hradec Kralove
ZIP/Postal Code
500 05
Country
Czechia
Facility Name
Research Site
City
Hradec Kralove
ZIP/Postal Code
50003
Country
Czechia
Facility Name
Research Site
City
Jihlava
ZIP/Postal Code
58633
Country
Czechia
Facility Name
Research Site
City
Prague 5
ZIP/Postal Code
150 06
Country
Czechia
Facility Name
Research Site
City
Teplice
ZIP/Postal Code
41529
Country
Czechia
Facility Name
Research Site
City
Bydgoszcz
ZIP/Postal Code
85-654
Country
Poland
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-595
Country
Poland
Facility Name
Research Site
City
Katowice
ZIP/Postal Code
40-650
Country
Poland
Facility Name
Research Site
City
Lodz
ZIP/Postal Code
90-324
Country
Poland
Facility Name
Research Site
City
Lublin
ZIP/Postal Code
20-605
Country
Poland
Facility Name
Research Site
City
Oswiecim
ZIP/Postal Code
32-600
Country
Poland
Facility Name
Research Site
City
Plewiska
ZIP/Postal Code
62-064
Country
Poland
Facility Name
Research Site
City
Poznan
ZIP/Postal Code
61-853
Country
Poland
Facility Name
Research Site
City
Rzeszow
ZIP/Postal Code
35-055
Country
Poland
Facility Name
Research Site
City
Warszawa
ZIP/Postal Code
01-697
Country
Poland
Facility Name
Research Site
City
Kazan
ZIP/Postal Code
420021
Country
Russian Federation
Facility Name
Research Site
City
Krasnoyarsk
ZIP/Postal Code
660037
Country
Russian Federation
Facility Name
Research Site
City
Krasnoyarsk
ZIP/Postal Code
660049
Country
Russian Federation
Facility Name
Research Site
City
Moscow
ZIP/Postal Code
129128
Country
Russian Federation
Facility Name
Research Site
City
Novosibirsk
ZIP/Postal Code
630102
Country
Russian Federation
Facility Name
Research Site
City
Perm
ZIP/Postal Code
614000
Country
Russian Federation
Facility Name
Research Site
City
Saransk
ZIP/Postal Code
430032
Country
Russian Federation
Facility Name
Research Site
City
Belgrade
ZIP/Postal Code
11000
Country
Serbia
Facility Name
Research Site
City
Kragujevac
ZIP/Postal Code
34000
Country
Serbia
Facility Name
Research Site
City
Nis
ZIP/Postal Code
18000
Country
Serbia
Facility Name
Research Site
City
Uzice
ZIP/Postal Code
31000
Country
Serbia
Facility Name
Research Site
City
Banska Bystrica
ZIP/Postal Code
97404
Country
Slovakia
Facility Name
Research Site
City
Bratislava
ZIP/Postal Code
85101
Country
Slovakia
Facility Name
Research Site
City
Dubnica nad Vahom
ZIP/Postal Code
01841
Country
Slovakia
Facility Name
Research Site
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08003
Country
Spain
Facility Name
Research Site
City
Barcelona
ZIP/Postal Code
08035
Country
Spain
Facility Name
Research Site
City
Chernivtsi
ZIP/Postal Code
58018
Country
Ukraine
Facility Name
Research Site
City
Ivano-Frankivsk
ZIP/Postal Code
76008
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
ZIP/Postal Code
61058
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
ZIP/Postal Code
61068
Country
Ukraine
Facility Name
Research Site
City
Kharkiv
ZIP/Postal Code
61103
Country
Ukraine
Facility Name
Research Site
City
Kyiv
ZIP/Postal Code
01601
Country
Ukraine
Facility Name
Research Site
City
Kyiv
ZIP/Postal Code
03110
Country
Ukraine
Facility Name
Research Site
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Facility Name
Research Site
City
Poltava
ZIP/Postal Code
36011
Country
Ukraine
Facility Name
Research Site
City
Zaporizhzhia
ZIP/Postal Code
69035
Country
Ukraine
Facility Name
Research Site
City
Zaporizhzhia
ZIP/Postal Code
69600
Country
Ukraine

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing 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
IPD Sharing 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.
IPD Sharing URL
https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Citations:
PubMed Identifier
31075187
Citation
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.
Results Reference
result
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527-0086
Description
Trial Awareness and Transparency website

Learn more about this trial

A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis

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