<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02975349</url>
  </required_header>
  <id_info>
    <org_study_id>MS200527-0086</org_study_id>
    <secondary_id>2016-001448-21</secondary_id>
    <nct_id>NCT02975349</nct_id>
  </id_info>
  <brief_title>A Study of Efficacy and Safety of M2951 in Participants With Relapsing Multiple Sclerosis</brief_title>
  <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.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EMD Serono Research &amp; Development Institute, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>EMD Serono</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this protocol is to find out about the safety and effectiveness of M2951 in&#xD;
      participants with relapsing multiple sclerosis. Participants were placed into 1 of 3 groups&#xD;
      to receive M2951, placebo or tecfidera for 24 weeks. After 24 weeks, the participants on&#xD;
      placebo were given M2951.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">March 7, 2017</start_date>
  <completion_date type="Anticipated">February 15, 2025</completion_date>
  <primary_completion_date type="Actual">January 24, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Total Number of Gadolinium-Enhancing T1 Lesions</measure>
    <time_frame>Week 12 to Week 24</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Annualized Relapse Rate (ARR) at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualified Relapse-Free Status at Week 24</measure>
    <time_frame>Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death</measure>
    <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)</measure>
    <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values</measure>
    <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
    <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 &gt;= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)</measure>
    <time_frame>Baseline (Day 1), Weeks 4, 16, and 24</time_frame>
    <description>Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)</measure>
    <time_frame>Weeks 48</time_frame>
    <description>Absolute Concentrations serum levels of IgG, IgA, IgM were to be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)</measure>
    <time_frame>Baseline (Day 1), Weeks 4, 16, and 24</time_frame>
    <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)</measure>
    <time_frame>Baseline (Day 1), Week 48</time_frame>
    <description>Change in the serum levels of IgG, IgA, IgM were to be assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Numbers of B Cells (Active Treatment Period)</measure>
    <time_frame>Baseline (Day 1), Weeks 4, and 24</time_frame>
    <description>Absolute Numbers of B Cells are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Absolute Numbers of B Cells (Blinded Extension Period)</measure>
    <time_frame>Weeks 48 and 52</time_frame>
    <description>Absolute Numbers of B Cells to be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Absolute B Cells (Active Treatment Period)</measure>
    <time_frame>Baseline (Day 1), Weeks 4, and 24</time_frame>
    <description>Change from baseline in absolute B cells are reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Absolute B Cells (Blinded Extension Period)</measure>
    <time_frame>Weeks 48 and 52</time_frame>
    <description>Change from baseline in absolute B cells to be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of New Gadolinium-positive (Gd+) T1 Lesions</measure>
    <time_frame>Week 12 to 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions</measure>
    <time_frame>Week 12 to Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of New or Enlarging T2 Lesions</measure>
    <time_frame>Week 12 to Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Volume of T2 Lesions at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24</measure>
    <time_frame>Baseline, Week 24</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48</measure>
    <time_frame>Week 48</time_frame>
    <description>Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48</measure>
    <time_frame>Week 48</time_frame>
    <description>Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Annualized Relapse Rate (ARR)</measure>
    <time_frame>Week 0 to Week 48</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Qualified Relapse-free Status</measure>
    <time_frame>Week 25 to Week 48</time_frame>
    <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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48</measure>
    <time_frame>Week 24, Week 48</time_frame>
    <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).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24</measure>
    <time_frame>Week 24 to Week 48</time_frame>
    <description>Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48</measure>
    <time_frame>Week 24, Week 48</time_frame>
    <description>Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Week 24 in Volume of T2 Lesions at Week 48</measure>
    <time_frame>Week 24, Week 48</time_frame>
    <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">267</enrollment>
  <condition>Relapsing-remitting Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Placebo then Evobrutinib 25 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Evobrutinib 25 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Evobrutinib 75 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Evobrutinib 75 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tecfidera</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <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.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Evobrutinib</intervention_name>
    <description>Participants received Evobrutinib 75 milligrams (mg) orally, twice daily (BID) up to Week 48</description>
    <arm_group_label>Evobrutinib 75 mg BID</arm_group_label>
    <other_name>M2951</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Evobrutinib</intervention_name>
    <description>Participants received Evobrutinib 25 mg orally, once daily (QD) up to Week 48</description>
    <arm_group_label>Evobrutinib 25 mg QD</arm_group_label>
    <other_name>M2951</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Evobrutinib</intervention_name>
    <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48</description>
    <arm_group_label>Evobrutinib 75 mg QD</arm_group_label>
    <other_name>M2951</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo were administered for 24 weeks</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Placebo then Evobrutinib 25 mg QD</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tecfidera</intervention_name>
    <description>Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (48 weeks).</description>
    <arm_group_label>Tecfidera</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Evobrutinib</intervention_name>
    <description>Following Placebo for 24 weeks, participants received Evobrutinib 25 milligram (mg) orally, once daily (QD) from Week 24 to 48 weeks.</description>
    <arm_group_label>Placebo then Evobrutinib 25 mg QD</arm_group_label>
    <other_name>M2951</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants with a diagnosis of relapsing multiple sclerosis (may include&#xD;
             participants with Secondary Progressive Multiple Sclerosis (SPMS) with superimposed&#xD;
             relapses provided they meet the other criteria) in accordance with revised McDonald&#xD;
             criteria for MS and Lublin and Reingold&#xD;
&#xD;
          -  Male or female aged 18 to 65 years&#xD;
&#xD;
          -  One or more documented relapses within the 2 years before Screening with either: a)&#xD;
             One relapse which occurred within the last year prior to randomization or b) the&#xD;
             presence of at least 1 gadolinium-positive (Gd+) T1 lesion within 6 months prior to&#xD;
             randomization would make the patient eligible.&#xD;
&#xD;
          -  Expanded Disability Status Scale score of 0 to 6 at Baseline&#xD;
&#xD;
          -  Women of childbearing potential must use a supplementary barrier method together with&#xD;
             a highly effective method of contraception (according to International Council for&#xD;
             Harmonisation [ICH] guidance M3[R2]) for 4 weeks prior to randomization, throughout&#xD;
             the trial, and for 90 days after the last dose of IMP.&#xD;
&#xD;
          -  Signed and dated informed consent (participant must be able to understand the informed&#xD;
             consent) indicating that the participant has been informed of all the pertinent&#xD;
             aspects of the trial prior to enrolment and will comply with the requirements of the&#xD;
             protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Progressive MS&#xD;
&#xD;
          -  Disease duration &gt; 15 years in participants with EDSS of 2 or less&#xD;
&#xD;
          -  Use of the following, as determined in the protocol ; rituximab, ocrelizumab,&#xD;
             mitoxantrone, or lymphocyte-depleting therapies, lymphocyte trafficking blockers (eg,&#xD;
             natalizumab, fingolimod), intravenous (IV) immunoglobulins (Ig), plasmapheresis,&#xD;
             immunosuppressive treatments, B-interferons or glatiramer acetate, Systemic&#xD;
             glucocorticoids, teriflunomide&#xD;
&#xD;
          -  Exposure to Tecfidera within 6 months prior to randomization&#xD;
&#xD;
          -  Any allergy, contraindication, or inability to tolerate Tecfidera&#xD;
&#xD;
          -  Treatment with dalfampridine (fampridine, Ampyra) unless on a stable dose for ≥ 30&#xD;
             days prior to randomization&#xD;
&#xD;
          -  Inability to comply with MRI scanning&#xD;
&#xD;
          -  Immunologic disorder other than MS, with the exception of secondary well-controlled&#xD;
             diabetes or thyroid disorder, or any other condition requiring oral, IV,&#xD;
             intramuscular, or intra-articular corticosteroid therapy&#xD;
&#xD;
          -  Vaccination with live or live-attenuated virus vaccine within 1 month prior to&#xD;
             Screening&#xD;
&#xD;
          -  Severe drug allergy or history of anaphylaxis, or allergy to the IMP or any of its&#xD;
             incipients&#xD;
&#xD;
          -  Active, clinically significant viral, bacterial, or fungal infection, or any major&#xD;
             episode of infection requiring hospitalization or treatment with parenteral&#xD;
             anti-infectives within 4 weeks of Screening, or completion of oral anti-infectives&#xD;
             within 2 weeks before or during Screening, or a history of recurrent infections (ie, 3&#xD;
             or more of the same type of infection in a 12-month rolling period). Vaginal&#xD;
             candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the&#xD;
             Investigator to be sufficiently controlled would not be exclusionary.&#xD;
&#xD;
          -  History of or positive testing for human immunodeficiency virus (HIV), hepatitis C&#xD;
             (HCV) antibody and/or polymerase chain reaction, hepatitis B surface antigen (HBsAg)&#xD;
             (+) and/or hepatitis B core total, and/or immunoglobulin M (IgM) antibody (+) at&#xD;
             Screening.&#xD;
&#xD;
          -  The participant: • Has a history of or current diagnosis of active tuberculosis (TB)&#xD;
             or • Is currently undergoing treatment for latent TB infection (LTBI) or • Has an&#xD;
             untreated LTBI or • Has a positive QuantiFERON®-TB test at Screening.&#xD;
&#xD;
          -  Indeterminate QuantiFERON®&#xD;
&#xD;
          -  Participants with current household contacts with active TB will also be excluded&#xD;
&#xD;
          -  History of splenectomy or any major surgery within 2 months prior to Screening&#xD;
&#xD;
          -  History of myocardial infarction or cerebrovascular event as per the protocol&#xD;
&#xD;
          -  History of attempted suicide within 6 months prior to Screening or a positive response&#xD;
             to items 4 or 5 of Columbia-Suicide Severity Rating Scale (C-SSRS)&#xD;
&#xD;
          -  An episode of major depression within the last 6 months prior to Screening&#xD;
&#xD;
          -  On anticoagulation, fish oil supplements, or antiplatelet therapy other than daily&#xD;
             aspirin for cardioprotection and treatment of Tecfidera induced flushing&#xD;
&#xD;
          -  History of cancer, except adequately treated basal cell or squamous cell carcinoma of&#xD;
             the skin&#xD;
&#xD;
          -  Breastfeeding/lactating or pregnant women&#xD;
&#xD;
          -  Participation in any investigational drug trial within 1 month or 5 half-lives of the&#xD;
             investigational drug, whichever is longest, prior to Screening&#xD;
&#xD;
          -  Participants currently receiving (or unable to stop using prior to receiving the first&#xD;
             dose of IMP) medications or herbal supplements known to be potent inhibitors of&#xD;
             cytochrome P450 3A (CYP3A)&#xD;
&#xD;
          -  History of or current alcohol or substance abuse&#xD;
&#xD;
          -  Clinically significant abnormality on electrocardiogram or screening chest X-ray&#xD;
&#xD;
          -  Clinically significant laboratory abnormality&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Blagoevgrad</city>
        <zip>2700</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dupnitsa</city>
        <zip>2600</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 1</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site 2</name>
      <address>
        <city>Pleven</city>
        <zip>5800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ruse</city>
        <zip>7002</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1142</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1309</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1336</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1407</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1606</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Sofia</city>
        <zip>1797</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Brno</city>
        <zip>656 91</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>500 05</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Hradec Kralove</city>
        <zip>50003</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Jihlava</city>
        <zip>58633</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Prague 5</city>
        <zip>150 06</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Teplice</city>
        <zip>41529</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bydgoszcz</city>
        <zip>85-654</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Katowice</city>
        <zip>40-595</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Katowice</city>
        <zip>40-650</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lodz</city>
        <zip>90-324</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lublin</city>
        <zip>20-605</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Oswiecim</city>
        <zip>32-600</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Plewiska</city>
        <zip>62-064</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Poznan</city>
        <zip>61-853</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Rzeszow</city>
        <zip>35-055</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Warszawa</city>
        <zip>01-697</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kazan</city>
        <zip>420021</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krasnoyarsk</city>
        <zip>660037</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Krasnoyarsk</city>
        <zip>660049</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Moscow</city>
        <zip>129128</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630102</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Perm</city>
        <zip>614000</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Saransk</city>
        <zip>430032</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kragujevac</city>
        <zip>34000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Nis</city>
        <zip>18000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Uzice</city>
        <zip>31000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Banska Bystrica</city>
        <zip>97404</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Bratislava</city>
        <zip>85101</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Dubnica nad Vahom</city>
        <zip>01841</zip>
        <country>Slovakia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>A Coruña</city>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Chernivtsi</city>
        <zip>58018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Ivano-Frankivsk</city>
        <zip>76008</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv</city>
        <zip>61058</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv</city>
        <zip>61068</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kharkiv</city>
        <zip>61103</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <zip>01601</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Kyiv</city>
        <zip>03110</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Lviv</city>
        <zip>79010</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Poltava</city>
        <zip>36011</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69035</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Site</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69600</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Bulgaria</country>
    <country>Czechia</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>Slovakia</country>
    <country>Spain</country>
    <country>Ukraine</country>
  </location_countries>
  <removed_countries>
    <country>Germany</country>
    <country>United States</country>
  </removed_countries>
  <link>
    <url>https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527-0086</url>
    <description>Trial Awareness and Transparency website</description>
  </link>
  <results_reference>
    <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.</citation>
    <PMID>31075187</PMID>
  </results_reference>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>November 23, 2016</study_first_submitted>
  <study_first_submitted_qc>November 23, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 29, 2016</study_first_posted>
  <results_first_submitted>January 13, 2021</results_first_submitted>
  <results_first_submitted_qc>January 13, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 5, 2021</results_first_posted>
  <disposition_first_submitted>January 14, 2019</disposition_first_submitted>
  <disposition_first_submitted_qc>January 14, 2019</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">January 17, 2019</disposition_first_posted>
  <last_update_submitted>May 17, 2023</last_update_submitted>
  <last_update_submitted_qc>May 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>M2951</keyword>
  <keyword>Relapsing Multiple Sclerosis</keyword>
  <keyword>Bruton's Tyrosine Kinase inhibitor</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Multiple Sclerosis, Relapsing-Remitting</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dimethyl Fumarate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_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_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_info_type>Analytic Code</ipd_info_type>
    <ipd_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_time_frame>
    <ipd_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_access_criteria>
    <ipd_url>https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>May 29, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/49/NCT02975349/Prot_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 14, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/49/NCT02975349/SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>The study consisted of a 24-week active treatment period, 24-week blinded extension (BE) period and a 96-week open-label extension period. Primary and secondary outcome measures were planned to be analyzed for active treatment and blinded extension period only. Open-label extension period is ongoing. Primary completion was achieved based on Active treatment period. Complete results will be updated within 1 year of study completion date.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
        </group>
        <group group_id="P2">
          <title>Placebo Then Evobrutinib 25 mg QD</title>
          <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.</description>
        </group>
        <group group_id="P3">
          <title>Evobrutinib 25 mg QD</title>
          <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="P4">
          <title>Evobrutinib 75 mg QD</title>
          <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="P5">
          <title>Evobrutinib 75 mg BID</title>
          <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="P6">
          <title>Tecfidera</title>
          <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.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Active Treatment Period (24 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="54"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="52"/>
                <participants group_id="P4" count="53"/>
                <participants group_id="P5" count="54"/>
                <participants group_id="P6" count="54"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="49"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="47"/>
                <participants group_id="P4" count="48"/>
                <participants group_id="P5" count="48"/>
                <participants group_id="P6" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="5"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="6"/>
                <participants group_id="P6" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Un-specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Blinded Extension Period (24 Weeks)</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="49"/>
                <participants group_id="P3" count="47"/>
                <participants group_id="P4" count="48"/>
                <participants group_id="P5" count="48"/>
                <participants group_id="P6" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="42"/>
                <participants group_id="P3" count="43"/>
                <participants group_id="P4" count="44"/>
                <participants group_id="P5" count="46"/>
                <participants group_id="P6" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="7"/>
                <participants group_id="P3" count="4"/>
                <participants group_id="P4" count="4"/>
                <participants group_id="P5" count="2"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="2"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="2"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Progressive Disease</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Un-specified</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="0"/>
                <participants group_id="P6" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>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 &quot;as randomized&quot; 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.</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
        </group>
        <group group_id="B2">
          <title>Evobrutinib 25 mg QD</title>
          <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="B3">
          <title>Evobrutinib 75 mg QD</title>
          <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="B4">
          <title>Evobrutinib 75 mg BID</title>
          <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="B5">
          <title>Tecfidera</title>
          <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.</description>
        </group>
        <group group_id="B6">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="53"/>
            <count group_id="B2" value="50"/>
            <count group_id="B3" value="51"/>
            <count group_id="B4" value="53"/>
            <count group_id="B5" value="54"/>
            <count group_id="B6" value="261"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="41.6" spread="10.77"/>
                    <measurement group_id="B2" value="42.4" spread="9.37"/>
                    <measurement group_id="B3" value="42.9" spread="10.07"/>
                    <measurement group_id="B4" value="42.2" spread="11.50"/>
                    <measurement group_id="B5" value="42.8" spread="11.70"/>
                    <measurement group_id="B6" value="42.4" spread="10.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="39"/>
                    <measurement group_id="B2" value="32"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="36"/>
                    <measurement group_id="B5" value="39"/>
                    <measurement group_id="B6" value="181"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="16"/>
                    <measurement group_id="B4" value="17"/>
                    <measurement group_id="B5" value="15"/>
                    <measurement group_id="B6" value="80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                    <measurement group_id="B5" value="2"/>
                    <measurement group_id="B6" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="52"/>
                    <measurement group_id="B2" value="49"/>
                    <measurement group_id="B3" value="51"/>
                    <measurement group_id="B4" value="52"/>
                    <measurement group_id="B5" value="52"/>
                    <measurement group_id="B6" value="256"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="53"/>
                    <measurement group_id="B2" value="50"/>
                    <measurement group_id="B3" value="51"/>
                    <measurement group_id="B4" value="53"/>
                    <measurement group_id="B5" value="54"/>
                    <measurement group_id="B6" value="261"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="0"/>
                    <measurement group_id="B6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Total Number of Gadolinium-Enhancing T1 Lesions</title>
        <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.</description>
        <time_frame>Week 12 to Week 24</time_frame>
        <population>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 &quot;as randomized&quot; 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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of Gadolinium-Enhancing T1 Lesions</title>
          <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.</description>
          <population>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 &quot;as randomized&quot; 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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.85" spread="5.436"/>
                    <measurement group_id="O2" value="4.06" spread="8.024"/>
                    <measurement group_id="O3" value="1.69" spread="4.693"/>
                    <measurement group_id="O4" value="1.15" spread="3.702"/>
                    <measurement group_id="O5" value="4.78" spread="22.045"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2947</p_value>
            <method>Negative Binomial model</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>1.45</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.72</ci_lower_limit>
            <ci_upper_limit>2.91</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0015</p_value>
            <method>Negative Binomial model</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>0.30</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.14</ci_lower_limit>
            <ci_upper_limit>0.63</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0313</p_value>
            <method>Negative Binomial model</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>0.44</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.21</ci_lower_limit>
            <ci_upper_limit>0.93</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Relapse Rate (ARR) at Week 24</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Relapse Rate (ARR) at Week 24</title>
          <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.</description>
          <population>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.</population>
          <units>relapses per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.37" lower_limit="0.17" upper_limit="0.70"/>
                    <measurement group_id="O2" value="0.57" lower_limit="0.30" upper_limit="0.97"/>
                    <measurement group_id="O3" value="0.13" lower_limit="0.03" upper_limit="0.38"/>
                    <measurement group_id="O4" value="0.08" lower_limit="0.01" upper_limit="0.30"/>
                    <measurement group_id="O5" value="0.20" lower_limit="0.06" upper_limit="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2692</p_value>
            <method>Negative Binomial model</method>
            <param_type>Qualified relapse rate ratio</param_type>
            <param_value>1.66</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.67</ci_lower_limit>
            <ci_upper_limit>4.09</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0896</p_value>
            <method>Negative Binomial model</method>
            <param_type>Qualified relapse rate ratio</param_type>
            <param_value>0.31</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.08</ci_lower_limit>
            <ci_upper_limit>1.20</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0633</p_value>
            <method>Negative Binomial model</method>
            <param_type>Qualified relapse rate ratio</param_type>
            <param_value>0.23</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.05</ci_lower_limit>
            <ci_upper_limit>1.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Qualified Relapse-Free Status at Week 24</title>
        <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.</description>
        <time_frame>Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Qualified Relapse-Free Status at Week 24</title>
          <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.</description>
          <population>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.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="77.4" lower_limit="63.8" upper_limit="87.7"/>
                    <measurement group_id="O2" value="74.0" lower_limit="59.7" upper_limit="85.4"/>
                    <measurement group_id="O3" value="88.2" lower_limit="76.1" upper_limit="95.6"/>
                    <measurement group_id="O4" value="86.8" lower_limit="74.7" upper_limit="94.5"/>
                    <measurement group_id="O5" value="88.9" lower_limit="77.4" upper_limit="95.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5609</p_value>
            <method>Logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>0.75</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.29</ci_lower_limit>
            <ci_upper_limit>1.95</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0689</p_value>
            <method>Logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.79</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.92</ci_lower_limit>
            <ci_upper_limit>8.41</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.1767</p_value>
            <method>Logistic model</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>2.08</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.72</ci_lower_limit>
            <ci_upper_limit>5.99</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24</title>
        <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.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>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 &quot;as randomized&quot; 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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24</title>
          <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.</description>
          <population>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 &quot;as randomized&quot; 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.</population>
          <units>Units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.301"/>
                    <measurement group_id="O2" value="0.02" spread="0.622"/>
                    <measurement group_id="O3" value="-0.14" spread="0.664"/>
                    <measurement group_id="O4" value="0.04" spread="0.216"/>
                    <measurement group_id="O5" value="0.02" spread="0.274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4070</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.5829</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.2732</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.00</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death</title>
        <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.</description>
        <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O6">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death</title>
          <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.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="49"/>
                <count group_id="O3" value="52"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
                <count group_id="O6" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24"/>
                    <measurement group_id="O2" value="19"/>
                    <measurement group_id="O3" value="28"/>
                    <measurement group_id="O4" value="35"/>
                    <measurement group_id="O5" value="34"/>
                    <measurement group_id="O6" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="4"/>
                    <measurement group_id="O6" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>TEAEs Leading to Death</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)</title>
        <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.</description>
        <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O6">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)</title>
          <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.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="49"/>
                <count group_id="O3" value="52"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
                <count group_id="O6" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Vital Sign Abnormalities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>ECG Abnormalities</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values</title>
        <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 &gt;= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.</description>
        <time_frame>Baseline up to Safety Follow-up (Week 52)</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O6">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values</title>
          <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 &gt;= 2 upper limit of normal (ULN), or a value classified as ++ Increasing were reported.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose of evobrutinib or placebo or Tecfidera.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="49"/>
                <count group_id="O3" value="52"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
                <count group_id="O6" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade &gt;= 3 hematology values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="1"/>
                    <measurement group_id="O5" value="0"/>
                    <measurement group_id="O6" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade &gt;= 3 biochemistry values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="6"/>
                    <measurement group_id="O4" value="9"/>
                    <measurement group_id="O5" value="16"/>
                    <measurement group_id="O6" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade &gt;= 3 or value &gt;= 2 ULN or ++ Increasing urinalysis values</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="2"/>
                    <measurement group_id="O5" value="2"/>
                    <measurement group_id="O6" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)</title>
        <description>Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.</description>
        <time_frame>Baseline (Day 1), Weeks 4, 16, and 24</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)</title>
          <description>Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
          <units>Gram per Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="52"/>
                <count group_id="O3" value="53"/>
                <count group_id="O4" value="54"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ig A, Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="51"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.99" spread="0.777"/>
                    <measurement group_id="O2" value="1.89" spread="0.764"/>
                    <measurement group_id="O3" value="1.90" spread="0.722"/>
                    <measurement group_id="O4" value="1.87" spread="0.675"/>
                    <measurement group_id="O5" value="2.03" spread="0.763"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig A, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="52"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.98" spread="0.777"/>
                    <measurement group_id="O2" value="1.92" spread="0.770"/>
                    <measurement group_id="O3" value="1.93" spread="0.762"/>
                    <measurement group_id="O4" value="1.94" spread="0.748"/>
                    <measurement group_id="O5" value="1.90" spread="0.699"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig A, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="53"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.07" spread="0.824"/>
                    <measurement group_id="O2" value="2.10" spread="0.813"/>
                    <measurement group_id="O3" value="2.13" spread="0.832"/>
                    <measurement group_id="O4" value="2.08" spread="0.753"/>
                    <measurement group_id="O5" value="2.03" spread="0.752"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig A, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="47"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.99" spread="0.807"/>
                    <measurement group_id="O2" value="2.12" spread="0.833"/>
                    <measurement group_id="O3" value="2.09" spread="0.838"/>
                    <measurement group_id="O4" value="2.09" spread="0.793"/>
                    <measurement group_id="O5" value="1.97" spread="0.757"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="51"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.61" spread="1.897"/>
                    <measurement group_id="O2" value="9.43" spread="2.126"/>
                    <measurement group_id="O3" value="9.81" spread="1.841"/>
                    <measurement group_id="O4" value="9.62" spread="1.960"/>
                    <measurement group_id="O5" value="9.47" spread="1.839"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="52"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.64" spread="2.094"/>
                    <measurement group_id="O2" value="9.34" spread="1.972"/>
                    <measurement group_id="O3" value="9.79" spread="1.910"/>
                    <measurement group_id="O4" value="9.64" spread="1.987"/>
                    <measurement group_id="O5" value="9.05" spread="1.922"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="53"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.68" spread="2.085"/>
                    <measurement group_id="O2" value="9.41" spread="2.077"/>
                    <measurement group_id="O3" value="9.70" spread="1.991"/>
                    <measurement group_id="O4" value="9.56" spread="2.129"/>
                    <measurement group_id="O5" value="9.58" spread="1.850"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="47"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.66" spread="2.081"/>
                    <measurement group_id="O2" value="9.46" spread="2.123"/>
                    <measurement group_id="O3" value="9.62" spread="2.048"/>
                    <measurement group_id="O4" value="9.36" spread="1.988"/>
                    <measurement group_id="O5" value="9.27" spread="1.866"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="51"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.42" spread="0.692"/>
                    <measurement group_id="O2" value="1.27" spread="0.542"/>
                    <measurement group_id="O3" value="1.44" spread="0.716"/>
                    <measurement group_id="O4" value="1.33" spread="0.684"/>
                    <measurement group_id="O5" value="1.27" spread="0.589"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="51"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.40" spread="0.668"/>
                    <measurement group_id="O2" value="1.21" spread="0.526"/>
                    <measurement group_id="O3" value="1.32" spread="0.654"/>
                    <measurement group_id="O4" value="1.28" spread="0.656"/>
                    <measurement group_id="O5" value="1.23" spread="0.603"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="53"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.43" spread="0.703"/>
                    <measurement group_id="O2" value="1.13" spread="0.558"/>
                    <measurement group_id="O3" value="1.24" spread="0.639"/>
                    <measurement group_id="O4" value="1.20" spread="0.689"/>
                    <measurement group_id="O5" value="1.28" spread="0.678"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="47"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.44" spread="0.748"/>
                    <measurement group_id="O2" value="1.03" spread="0.499"/>
                    <measurement group_id="O3" value="1.20" spread="0.672"/>
                    <measurement group_id="O4" value="1.08" spread="0.494"/>
                    <measurement group_id="O5" value="1.29" spread="0.667"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)</title>
        <description>Absolute Concentrations serum levels of IgG, IgA, IgM were to be assessed.</description>
        <time_frame>Weeks 48</time_frame>
        <posting_date>02/2026</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)</title>
        <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
        <time_frame>Baseline (Day 1), Weeks 4, 16, and 24</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)</title>
          <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
          <units>Gram per Liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="54"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="53"/>
                <count group_id="O4" value="54"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Ig A, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.201"/>
                    <measurement group_id="O2" value="0.02" spread="0.165"/>
                    <measurement group_id="O3" value="0.04" spread="0.169"/>
                    <measurement group_id="O4" value="0.07" spread="0.195"/>
                    <measurement group_id="O5" value="-0.13" spread="0.238"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig A, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="51"/>
                    <count group_id="O2" value="48"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.10" spread="0.188"/>
                    <measurement group_id="O2" value="0.18" spread="0.245"/>
                    <measurement group_id="O3" value="0.21" spread="0.313"/>
                    <measurement group_id="O4" value="0.22" spread="0.209"/>
                    <measurement group_id="O5" value="-0.02" spread="0.274"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig A, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="44"/>
                    <count group_id="O3" value="48"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.250"/>
                    <measurement group_id="O2" value="0.21" spread="0.283"/>
                    <measurement group_id="O3" value="0.18" spread="0.416"/>
                    <measurement group_id="O4" value="0.22" spread="0.229"/>
                    <measurement group_id="O5" value="-0.06" spread="0.207"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="0.758"/>
                    <measurement group_id="O2" value="-0.10" spread="0.697"/>
                    <measurement group_id="O3" value="-0.02" spread="0.688"/>
                    <measurement group_id="O4" value="0.02" spread="0.581"/>
                    <measurement group_id="O5" value="-0.42" spread="0.926"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="53"/>
                    <count group_id="O2" value="48"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" spread="0.747"/>
                    <measurement group_id="O2" value="-0.07" spread="0.964"/>
                    <measurement group_id="O3" value="-0.10" spread="1.068"/>
                    <measurement group_id="O4" value="-0.05" spread="0.710"/>
                    <measurement group_id="O5" value="0.07" spread="0.961"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig G, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="45"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.682"/>
                    <measurement group_id="O2" value="0.00" spread="1.228"/>
                    <measurement group_id="O3" value="-0.15" spread="1.058"/>
                    <measurement group_id="O4" value="-0.28" spread="0.774"/>
                    <measurement group_id="O5" value="-0.23" spread="0.882"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="54"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="54"/>
                    <count group_id="O5" value="54"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.210"/>
                    <measurement group_id="O2" value="-0.06" spread="0.100"/>
                    <measurement group_id="O3" value="-0.12" spread="0.233"/>
                    <measurement group_id="O4" value="-0.05" spread="0.133"/>
                    <measurement group_id="O5" value="-0.04" spread="0.132"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="53"/>
                    <count group_id="O2" value="48"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="0.177"/>
                    <measurement group_id="O2" value="-0.12" spread="0.184"/>
                    <measurement group_id="O3" value="-0.18" spread="0.244"/>
                    <measurement group_id="O4" value="-0.14" spread="0.189"/>
                    <measurement group_id="O5" value="-0.00" spread="0.184"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Ig M, Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="50"/>
                    <count group_id="O2" value="45"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="48"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.04" spread="0.163"/>
                    <measurement group_id="O2" value="-0.14" spread="0.286"/>
                    <measurement group_id="O3" value="-0.20" spread="0.289"/>
                    <measurement group_id="O4" value="-0.21" spread="0.167"/>
                    <measurement group_id="O5" value="-0.00" spread="0.186"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)</title>
        <description>Change in the serum levels of IgG, IgA, IgM were to be assessed.</description>
        <time_frame>Baseline (Day 1), Week 48</time_frame>
        <posting_date>02/2026</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Numbers of B Cells (Active Treatment Period)</title>
        <description>Absolute Numbers of B Cells are reported.</description>
        <time_frame>Baseline (Day 1), Weeks 4, and 24</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Absolute Numbers of B Cells (Active Treatment Period)</title>
          <description>Absolute Numbers of B Cells are reported.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
          <units>cells per micro-liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="52"/>
                <count group_id="O3" value="53"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Day 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                    <count group_id="O2" value="52"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="51"/>
                    <count group_id="O5" value="48"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="242" spread="134.2"/>
                    <measurement group_id="O2" value="208" spread="117.5"/>
                    <measurement group_id="O3" value="247" spread="131.8"/>
                    <measurement group_id="O4" value="219" spread="113.7"/>
                    <measurement group_id="O5" value="210" spread="97.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="243" spread="130.8"/>
                    <measurement group_id="O2" value="220" spread="92.7"/>
                    <measurement group_id="O3" value="277" spread="156.2"/>
                    <measurement group_id="O4" value="270" spread="143.2"/>
                    <measurement group_id="O5" value="201" spread="114.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="44"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="47"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="264" spread="154.9"/>
                    <measurement group_id="O2" value="230" spread="119.7"/>
                    <measurement group_id="O3" value="235" spread="115.3"/>
                    <measurement group_id="O4" value="214" spread="105.0"/>
                    <measurement group_id="O5" value="180" spread="114.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Absolute Numbers of B Cells (Blinded Extension Period)</title>
        <description>Absolute Numbers of B Cells to be reported.</description>
        <time_frame>Weeks 48 and 52</time_frame>
        <posting_date>02/2026</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Absolute B Cells (Active Treatment Period)</title>
        <description>Change from baseline in absolute B cells are reported.</description>
        <time_frame>Baseline (Day 1), Weeks 4, and 24</time_frame>
        <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Absolute B Cells (Active Treatment Period)</title>
          <description>Change from baseline in absolute B cells are reported.</description>
          <population>The safety analysis set included of all participants who received at least 1 dose evobrutinib or placebo or Tecfidera. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure and &quot;Number Analyzed&quot; signified those participants who were evaluable for the specified category at given time points.</population>
          <units>cells per micro-liter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="52"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="53"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="52"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="52"/>
                    <count group_id="O2" value="50"/>
                    <count group_id="O3" value="53"/>
                    <count group_id="O4" value="53"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-5" spread="94.5"/>
                    <measurement group_id="O2" value="9" spread="112.2"/>
                    <measurement group_id="O3" value="31" spread="114.2"/>
                    <measurement group_id="O4" value="50" spread="86.7"/>
                    <measurement group_id="O5" value="-3" spread="111.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="49"/>
                    <count group_id="O2" value="44"/>
                    <count group_id="O3" value="49"/>
                    <count group_id="O4" value="47"/>
                    <count group_id="O5" value="52"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" spread="135.8"/>
                    <measurement group_id="O2" value="13" spread="98.2"/>
                    <measurement group_id="O3" value="-15" spread="128.5"/>
                    <measurement group_id="O4" value="-9" spread="85.1"/>
                    <measurement group_id="O5" value="-26" spread="113.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Absolute B Cells (Blinded Extension Period)</title>
        <description>Change from baseline in absolute B cells to be reported.</description>
        <time_frame>Weeks 48 and 52</time_frame>
        <posting_date>02/2026</posting_date>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of New Gadolinium-positive (Gd+) T1 Lesions</title>
        <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.</description>
        <time_frame>Week 12 to 24</time_frame>
        <population>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 &quot;as randomized&quot; 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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of New Gadolinium-positive (Gd+) T1 Lesions</title>
          <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.</description>
          <population>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 &quot;as randomized&quot; 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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.08" spread="4.371"/>
                    <measurement group_id="O2" value="3.44" spread="6.846"/>
                    <measurement group_id="O3" value="1.20" spread="3.499"/>
                    <measurement group_id="O4" value="0.98" spread="3.273"/>
                    <measurement group_id="O5" value="3.24" spread="15.320"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.3676</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>1.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.70</ci_lower_limit>
            <ci_upper_limit>2.65</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0005</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>0.27</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.13</ci_lower_limit>
            <ci_upper_limit>0.57</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0157</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion rate ratio</param_type>
            <param_value>0.41</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.20</ci_lower_limit>
            <ci_upper_limit>0.85</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions</title>
        <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.</description>
        <time_frame>Week 12 to Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions</title>
          <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.</description>
          <population>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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" spread="1.439"/>
                    <measurement group_id="O2" value="1.31" spread="3.130"/>
                    <measurement group_id="O3" value="0.42" spread="1.173"/>
                    <measurement group_id="O4" value="0.34" spread="0.960"/>
                    <measurement group_id="O5" value="1.45" spread="7.293"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9731</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.25</ci_lower_limit>
            <ci_upper_limit>0.25</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0017</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>-0.25</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.50</ci_lower_limit>
            <ci_upper_limit>0.00</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>&lt; 0.0001</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>-0.50</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.75</ci_lower_limit>
            <ci_upper_limit>-0.25</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of New or Enlarging T2 Lesions</title>
        <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.</description>
        <time_frame>Week 12 to Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of New or Enlarging T2 Lesions</title>
          <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.</description>
          <population>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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.96" spread="6.994"/>
                    <measurement group_id="O2" value="6.52" spread="11.569"/>
                    <measurement group_id="O3" value="3.41" spread="10.752"/>
                    <measurement group_id="O4" value="2.19" spread="4.719"/>
                    <measurement group_id="O5" value="5.35" spread="16.667"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.4807</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion Rate ratio</param_type>
            <param_value>1.29</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.63</ci_lower_limit>
            <ci_upper_limit>2.65</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0620</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion Rate ratio</param_type>
            <param_value>0.50</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.24</ci_lower_limit>
            <ci_upper_limit>1.04</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0189</p_value>
            <method>Negative Binomial</method>
            <param_type>Lesion Rate ratio</param_type>
            <param_value>0.42</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.20</ci_lower_limit>
            <ci_upper_limit>0.87</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Volume of T2 Lesions at Week 24</title>
        <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>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, &quot;Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Volume of T2 Lesions at Week 24</title>
          <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans. Tecfidera treatment group was not included in inferential analysis.</description>
          <population>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, &quot;Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>cubic centimeter (cc)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="46"/>
                <count group_id="O3" value="48"/>
                <count group_id="O4" value="46"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.42" spread="1.009"/>
                    <measurement group_id="O2" value="0.93" spread="1.853"/>
                    <measurement group_id="O3" value="-0.01" spread="0.562"/>
                    <measurement group_id="O4" value="0.09" spread="0.463"/>
                    <measurement group_id="O5" value="0.47" spread="2.964"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.8776</p_value>
            <method>Mixed Effect Model for Repeat Measures</method>
            <param_type>Difference in least squares means</param_type>
            <param_value>0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.24</ci_lower_limit>
            <ci_upper_limit>0.28</ci_upper_limit>
            <estimate_desc>Difference in least squares means of change from baseline in cube root of volume measured in centimeter.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0019</p_value>
            <method>Mixed Effect Model for Repeat Measures</method>
            <param_type>Difference in least squares means</param_type>
            <param_value>-0.41</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.66</ci_lower_limit>
            <ci_upper_limit>-0.15</ci_upper_limit>
            <estimate_desc>Difference in least squares means of change from baseline in cube root of volume measured in centimeter.</estimate_desc>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0063</p_value>
            <method>Mixed Effect Model for Repeat Measures</method>
            <param_type>Difference in least squares means</param_type>
            <param_value>-0.36</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.62</ci_lower_limit>
            <ci_upper_limit>-0.10</ci_upper_limit>
            <estimate_desc>Difference in least squares means of change from baseline in cube root of volume measured in centimeter.</estimate_desc>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24</title>
        <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.</description>
        <time_frame>Baseline, Week 24</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24</title>
          <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.</description>
          <population>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.</population>
          <units>cc</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.023" spread="0.2220"/>
                    <measurement group_id="O2" value="0.057" spread="0.3479"/>
                    <measurement group_id="O3" value="-0.111" spread="0.5416"/>
                    <measurement group_id="O4" value="-0.051" spread="0.1032"/>
                    <measurement group_id="O5" value="-0.050" spread="0.4771"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.9315</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.004</ci_lower_limit>
            <ci_upper_limit>0.009</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0008</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>-0.014</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.050</ci_lower_limit>
            <ci_upper_limit>0.000</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <p_value>0.0014</p_value>
            <method>Wilcoxon rank-sum test</method>
            <param_type>Hodges-Lehmann estimate</param_type>
            <param_value>-0.018</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.042</ci_lower_limit>
            <ci_upper_limit>0.000</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
        <description>Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
        <time_frame>Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
          <description>Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
          <population>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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00" spread="1.614"/>
                    <measurement group_id="O2" value="1.91" spread="4.296"/>
                    <measurement group_id="O3" value="0.85" spread="2.867"/>
                    <measurement group_id="O4" value="0.49" spread="1.218"/>
                    <measurement group_id="O5" value="0.42" spread="1.444"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
        <description>Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
        <time_frame>Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
          <description>Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
          <population>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.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.95" spread="1.569"/>
                    <measurement group_id="O2" value="1.84" spread="4.154"/>
                    <measurement group_id="O3" value="0.85" spread="2.867"/>
                    <measurement group_id="O4" value="0.49" spread="1.218"/>
                    <measurement group_id="O5" value="0.42" spread="1.444"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Annualized Relapse Rate (ARR)</title>
        <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.</description>
        <time_frame>Week 0 to Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Annualized Relapse Rate (ARR)</title>
          <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.</description>
          <population>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.</population>
          <units>relapses per year</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="53"/>
                <count group_id="O2" value="50"/>
                <count group_id="O3" value="51"/>
                <count group_id="O4" value="53"/>
                <count group_id="O5" value="54"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.37" lower_limit="0.21" upper_limit="0.59"/>
                    <measurement group_id="O2" value="0.52" lower_limit="0.33" upper_limit="0.78"/>
                    <measurement group_id="O3" value="0.25" lower_limit="0.12" upper_limit="0.44"/>
                    <measurement group_id="O4" value="0.11" lower_limit="0.04" upper_limit="0.25"/>
                    <measurement group_id="O5" value="0.14" lower_limit="0.06" upper_limit="0.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Qualified Relapse-free Status</title>
        <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.</description>
        <time_frame>Week 25 to Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Qualified Relapse-free Status</title>
          <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.</description>
          <population>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.</population>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="84.1"/>
                    <measurement group_id="O2" value="86.4"/>
                    <measurement group_id="O3" value="78.3"/>
                    <measurement group_id="O4" value="91.1"/>
                    <measurement group_id="O5" value="96.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48</title>
        <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).</description>
        <time_frame>Week 24, Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48</title>
          <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).</description>
          <population>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.</population>
          <units>Units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.260"/>
                    <measurement group_id="O2" value="-0.10" spread="0.351"/>
                    <measurement group_id="O3" value="-0.01" spread="0.619"/>
                    <measurement group_id="O4" value="0.00" spread="0.238"/>
                    <measurement group_id="O5" value="-0.10" spread="0.404"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24</title>
        <description>Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
        <time_frame>Week 24 to Week 48</time_frame>
        <population>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, &quot;Number of Participants Analyzed&quot; signified those participants who were evaluable for this outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24</title>
          <description>Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
          <population>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, &quot;Number of Participants Analyzed&quot; signified those participants who were evaluable for this outcome measure.</population>
          <units>Lesions</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="42"/>
                <count group_id="O2" value="42"/>
                <count group_id="O3" value="43"/>
                <count group_id="O4" value="43"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.57" spread="4.346"/>
                    <measurement group_id="O2" value="5.86" spread="11.330"/>
                    <measurement group_id="O3" value="3.84" spread="10.083"/>
                    <measurement group_id="O4" value="1.60" spread="3.799"/>
                    <measurement group_id="O5" value="1.88" spread="4.796"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
        <description>Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
        <time_frame>Week 24, Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48</title>
          <description>Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.</description>
          <population>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.</population>
          <units>cc</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.092" spread="0.4626"/>
                    <measurement group_id="O2" value="0.088" spread="0.4006"/>
                    <measurement group_id="O3" value="0.045" spread="0.2285"/>
                    <measurement group_id="O4" value="0.024" spread="0.1981"/>
                    <measurement group_id="O5" value="-0.203" spread="1.1073"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Week 24 in Volume of T2 Lesions at Week 48</title>
        <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
        <time_frame>Week 24, Week 48</time_frame>
        <population>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.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo Then Evobrutinib 25 mg QD</title>
            <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.</description>
          </group>
          <group group_id="O2">
            <title>Evobrutinib 25 mg QD</title>
            <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O3">
            <title>Evobrutinib 75 mg QD</title>
            <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O4">
            <title>Evobrutinib 75 mg BID</title>
            <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
          </group>
          <group group_id="O5">
            <title>Tecfidera</title>
            <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.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Week 24 in Volume of T2 Lesions at Week 48</title>
          <description>Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.</description>
          <population>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.</population>
          <units>cc</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="44"/>
                <count group_id="O2" value="44"/>
                <count group_id="O3" value="46"/>
                <count group_id="O4" value="45"/>
                <count group_id="O5" value="50"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.53" spread="1.360"/>
                    <measurement group_id="O2" value="0.67" spread="1.865"/>
                    <measurement group_id="O3" value="0.35" spread="1.083"/>
                    <measurement group_id="O4" value="-0.03" spread="1.031"/>
                    <measurement group_id="O5" value="-0.57" spread="2.699"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline up to Safety Follow up of blinded extension period (Week 52)</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.</description>
        </group>
        <group group_id="E2">
          <title>Placebo Then Evobrutinib 25 mg QD</title>
          <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.</description>
        </group>
        <group group_id="E3">
          <title>Evobrutinib 25 mg QD (Period 1 and Period 2)</title>
          <description>Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="E4">
          <title>Evobrutinib 75 mg QD (Period 1 and Period 2)</title>
          <description>Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="E5">
          <title>Evobrutinib 75 mg BID (Period 1 and Period 2)</title>
          <description>Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.</description>
        </group>
        <group group_id="E6">
          <title>Tecfidera (Period 1 and Period 2)</title>
          <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.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatitis toxic</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Lyme disease</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Overdose</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Road traffic accident</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Transaminases increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Gastric cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Lung neoplasm</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Epilepsy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Restless legs syndrome</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Pregnancy, puerperium and perinatal conditions</title>
            <event_list>
              <event>
                <sub_title>Abortion spontaneous</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Peripheral embolism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 21.0</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="19" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="19" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="20" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="30" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Nasopharyngitis</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="7" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Cystitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="6" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Lipase increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="5" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="5" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="2" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Gamma-glutamyltransferase increased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="5" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>White blood cell count decreased</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="3" subjects_at_risk="54"/>
              </event>
              <event>
                <sub_title>Amylase increased</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="0" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="4" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="1" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="1" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Erythema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="7" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Flushing</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="49"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="52"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="53"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="54"/>
                <counts group_id="E6" subjects_affected="12" subjects_at_risk="54"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Reported p values are not adjusted for multiple testing.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Communication Center</name_or_title>
      <organization>Merck KGaA, Darmstadt, Germany</organization>
      <phone>+49-6151-72-5200</phone>
      <email>service@emdgroup.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02975349
org study id: MS200527-0086
secondary id: 2016-001448-21
nct id: NCT02975349
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Total Number of Gadolinium-Enhancing T1 Lesions
time frame: Week 12 to Week 24
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.
measure: Annualized Relapse Rate (ARR) at Week 24
time frame: 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.
measure: Qualified Relapse-Free Status at Week 24
time frame: 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.
measure: Change From Baseline in Expanded Disability Status Scale (EDSS) at Week 24
time frame: Baseline, 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.
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Death
time frame: Baseline up to Safety Follow-up (Week 52)
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.
measure: Number of Participants With Clinically Significant Changes From Baseline in Vital Signs and Electrocardiograms (ECGs)
time frame: Baseline up to Safety Follow-up (Week 52)
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.
measure: Number of Participants With Grade 3 or Higher Hematology, Biochemistry and Urinalysis Values
time frame: Baseline up to Safety Follow-up (Week 52)
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.
measure: Absolute Concentrations of Immunoglobulin (Ig) Levels (Active Treatment Period)
time frame: Baseline (Day 1), Weeks 4, 16, and 24
description: Absolute Concentrations serum levels of IgG, IgA, IgM were assessed.
measure: Absolute Concentrations of Immunoglobulin (Ig) Levels (Blinded Extension Period)
time frame: Weeks 48
description: Absolute Concentrations serum levels of IgG, IgA, IgM were to be assessed.
measure: Change From Baseline in Immunoglobulin (Ig) Levels (Active Treatment Period)
time frame: Baseline (Day 1), Weeks 4, 16, and 24
description: Change in the serum levels of IgG, IgA, IgM were assessed.
measure: Change From Baseline in Immunoglobulin (Ig) Levels (Blinded Extension Period)
time frame: Baseline (Day 1), Week 48
description: Change in the serum levels of IgG, IgA, IgM were to be assessed.
measure: Absolute Numbers of B Cells (Active Treatment Period)
time frame: Baseline (Day 1), Weeks 4, and 24
description: Absolute Numbers of B Cells are reported.
measure: Absolute Numbers of B Cells (Blinded Extension Period)
time frame: Weeks 48 and 52
description: Absolute Numbers of B Cells to be reported.
measure: Change From Baseline in Absolute B Cells (Active Treatment Period)
time frame: Baseline (Day 1), Weeks 4, and 24
description: Change from baseline in absolute B cells are reported.
measure: Change From Baseline in Absolute B Cells (Blinded Extension Period)
time frame: Weeks 48 and 52
description: Change from baseline in absolute B cells to be reported.
measure: Total Number of New Gadolinium-positive (Gd+) T1 Lesions
time frame: Week 12 to 24
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.
measure: Mean Per-scan Number of Gadolinium-positive (Gd+) T1 Lesions
time frame: Week 12 to Week 24
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.
measure: Total Number of New or Enlarging T2 Lesions
time frame: Week 12 to Week 24
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.
measure: Change From Baseline in Volume of T2 Lesions at Week 24
time frame: Baseline, 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.
measure: Change From Baseline in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 24
time frame: Baseline, 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.
measure: Number of Gadolinium-positive (Gd+) T1 Lesions at Week 48
time frame: Week 48
description: Analysis of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
measure: Number of New Gadolinium-positive (Gd+) T1 Lesions at Week 48
time frame: Week 48
description: Analysis of new Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
measure: Annualized Relapse Rate (ARR)
time frame: Week 0 to Week 48
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.
measure: Qualified Relapse-free Status
time frame: Week 25 to Week 48
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.
measure: Change From Week 24 in Expanded Disability Status Scale (EDSS) at Week 48
time frame: Week 24, 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).
measure: Total Number of New or Enlarging T2 Lesions at Week 48 Relative to Week 24
time frame: Week 24 to Week 48
description: Analysis of New or Enlarging T2 lesions was done using magnetic resonance imaging (MRI) scans.
measure: Change From Week 24 in Volume of Gadolinium-positive (Gd+) T1 Lesions at Week 48
time frame: Week 24, Week 48
description: Analysis of volume of Gd+ T1 lesions was done using magnetic resonance imaging (MRI) scans.
measure: Change From Week 24 in Volume of T2 Lesions at Week 48
time frame: Week 24, Week 48
description: Analysis of volume of T2 lesions was done using magnetic resonance imaging (MRI) scans.
arm group label: Placebo then Evobrutinib 25 mg QD
arm group type: Experimental
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 group label: Evobrutinib 25 mg QD
arm group type: Experimental
description: Participants received Evobrutinib 25 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
arm group label: Evobrutinib 75 mg QD
arm group type: Experimental
description: Participants received Evobrutinib 75 mg orally, QD up to Week 48 in active treatment period 1 and BE period.
arm group label: Evobrutinib 75 mg BID
arm group type: Experimental
description: Participants received Evobrutinib 75 mg orally, twice daily (BID) up to Week 48 in active treatment period 1 and BE period.
arm group label: Tecfidera
arm group type: Active Comparator
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 group label: Placebo
arm group type: Placebo Comparator
description: Participants received placebo matched to Evobrutinib tablet orally for 24 weeks in active treatment period 1.
intervention type: Drug
intervention name: Evobrutinib
description: Participants received Evobrutinib 75 milligrams (mg) orally, twice daily (BID) up to Week 48
arm group label: Evobrutinib 75 mg BID
other name: M2951
intervention type: Drug
intervention name: Evobrutinib
description: Participants received Evobrutinib 25 mg orally, once daily (QD) up to Week 48
arm group label: Evobrutinib 25 mg QD
other name: M2951
intervention type: Drug
intervention name: Evobrutinib
description: Participants received Evobrutinib 75 mg orally, QD up to Week 48
arm group label: Evobrutinib 75 mg QD
other name: M2951
intervention type: Drug
intervention name: Placebo
description: Placebo were administered for 24 weeks
arm group label: Placebo
arm group label: Placebo then Evobrutinib 25 mg QD
intervention type: Drug
intervention name: Tecfidera
description: Tecfidera; 120 mg hard capsule BID for 7 days then 240 mg hard capsule BID for duration of treatment (48 weeks).
arm group label: Tecfidera
intervention type: Drug
intervention name: Evobrutinib
description: Following Placebo for 24 weeks, participants received Evobrutinib 25 milligram (mg) orally, once daily (QD) from Week 24 to 48 weeks.
arm group label: Placebo then Evobrutinib 25 mg QD
other name: M2951
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: EMD Serono Inc., a business of Merck KGaA, Darmstadt, Germany
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country: Bulgaria
country: Czechia
country: Poland
country: Russian Federation
country: Serbia
country: Slovakia
country: Spain
country: Ukraine
country: Germany
country: United States
url: https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527-0086
description: Trial Awareness and Transparency website
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.
PMID: 31075187
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Multiple Sclerosis, Relapsing-Remitting
mesh term: Sclerosis
mesh term: Dimethyl Fumarate
sharing ipd: Yes
ipd 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 info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd info type: Analytic Code
ipd 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 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 url: https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
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reported events: 
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limitations and caveats: Reported p values are not adjusted for multiple testing.
point of contact: 