<clinical_study>
  <!-- This xml conforms to an XML Schema at:
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  <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/NCT03233230</url>
  </required_header>
  <id_info>
    <org_study_id>MS200527-0060</org_study_id>
    <secondary_id>2017-000384-32</secondary_id>
    <nct_id>NCT03233230</nct_id>
  </id_info>
  <brief_title>Phase IIb Study of Evobrutinib in Subjects With Rheumatoid Arthritis</brief_title>
  <official_title>A Phase IIb, Randomized, Double-blind Study in Subjects With Rheumatoid Arthritis Evaluating the Safety and Efficacy of Evobrutinib Compared With Placebo in Subjects With an Inadequate Response to Methotrexate</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 purpose of this study was to determine the efficacy, dose response, and safety of M52951&#xD;
      in participants with Rheumatoid Arthritis (RA), and to consider a dose to took forward into&#xD;
      Phase III development.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">September 23, 2019</completion_date>
  <primary_completion_date type="Actual">September 23, 2019</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants * 100.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [&lt;] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 &lt; 3.2 based on DAS28- hsCRP at Week 12 were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [&lt;] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (&lt;) 2.6 indicated clinical remission. Percentage of participants with low DAS28 &lt; 2.6 based on DAS28- hsCRP at Week 12 were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)</measure>
    <time_frame>Week 12</time_frame>
    <description>ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants * 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)</measure>
    <time_frame>Week 12</time_frame>
    <description>ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants * 100.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</measure>
    <time_frame>up to Week 16</time_frame>
    <description>Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</measure>
    <time_frame>up to Week 16</time_frame>
    <description>Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</measure>
    <time_frame>up to Week 16</time_frame>
    <description>Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters</measure>
    <time_frame>up to Week 16</time_frame>
    <description>Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings</measure>
    <time_frame>up to Week 16</time_frame>
    <description>12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16</measure>
    <time_frame>Baseline, Week 2, 4, 8, 12 and 16</time_frame>
    <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16</measure>
    <time_frame>Baseline, Week 2, 4, 8, 12 and 16</time_frame>
    <description>Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter [mg/dL]), and participant's global assessment (visual analog scale [VAS]: 0 centimeter (cm) [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were less than or equal to (&lt;=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=&lt;] 2.8 at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =&lt; 2.8 indicated clinical remission. Percentage of participants with CDAI score =&lt; 2.8 were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=&lt;] 3.3 at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =&lt; 3.3 indicated clinical remission. Percentage of participants with SDAI score =&lt; 3.3 at Week 12 were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12</measure>
    <time_frame>Week 12</time_frame>
    <description>EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP &gt;5.1, low disease activity: DAS28-CRP &lt;3.2, and remission: DAS28-CRP &lt;2.6. EULAR DAS28-CRP responder index: good (absolute: &lt;3.2 or &gt;1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: &gt;5.1 or &lt;0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire [HAQ], and C-reactive protein [CRP]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter [mg/L]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP &lt; 3.2 implied low disease activity and &gt;= 3.2 to &lt;= 5.1 implied moderate disease activity, &gt; 5.1 implied high disease activity. DAS28-hsCRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(hsCRP in mg/L +1) + 0.014* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12</measure>
    <time_frame>Baseline, Week 12</time_frame>
    <description>The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">390</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>M2951 25 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>M2951 75 mg QD</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>M2951 50 mg BID</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M2591 25 mg QD</intervention_name>
    <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
    <arm_group_label>M2951 25 mg QD</arm_group_label>
    <other_name>Evobrutinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M2951 75 mg QD</intervention_name>
    <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
    <arm_group_label>M2951 75 mg QD</arm_group_label>
    <other_name>Evobrutinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M2951 50 mg BID</intervention_name>
    <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
    <arm_group_label>M2951 50 mg BID</arm_group_label>
    <other_name>Evobrutinib</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  In Japan, if a participant is less than (&lt;) 20 years, the written informed consent&#xD;
             from the participant's parent or guardian will be required in addition to the&#xD;
             participant's written consent.&#xD;
&#xD;
          -  Confirmed diagnosis of RA according to 2010 ACR/EULAR RA classification criteria of at&#xD;
             least 6 months duration prior to Screening&#xD;
&#xD;
          -  Persistently active moderate to severe RA at both Screening and Randomization (if&#xD;
             significant surgical treatment of a joint has been performed, that joint cannot be&#xD;
             counted for entry or enrollment purposes), as defined by: &gt;= 6 swollen joints (of 66&#xD;
             assessed) and &gt;= 6 tender joints (of 68 assessed).&#xD;
&#xD;
          -  An hsCRP &gt;= 5.0 milligram/liter (mg/L) at Screening&#xD;
&#xD;
          -  Treatment for &gt;= 16 weeks with 7.5 to 25 mg/week Methotrexate (MTX) at a stable dose&#xD;
             and route of administration (oral or parenteral) for at least 8 weeks prior to dosing&#xD;
             with the Investigational Medicinal Product (IMP) and maintained throughout the trial&#xD;
&#xD;
          -  For participants entering the trial on MTX doses &lt; 15 mg/week (&lt; 10 mg/week in Japan),&#xD;
             there must be clear documentation in the medical record that higher doses of MTX were&#xD;
             not tolerated or that the dose of MTX is the highest acceptable dose based on local&#xD;
             clinical practice guidelines.&#xD;
&#xD;
          -  For MRI Sub-study participants, participants must have palpable synovitis of the wrist&#xD;
             and/or &gt;= 1 of metacarpophalangeal joints 1 to 5, defined as loss of bony contours&#xD;
             with palpable joint effusion and/or swelling, in the MRI-designated hand (that is.,&#xD;
             the hand being used in MRI assessments).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  ACR functional class IV as defined by the ACR classification of functional status or&#xD;
             wheelchair/bedbound&#xD;
&#xD;
          -  Use of oral corticosteroids greater than (&gt;) 10 mg daily prednisone equivalent, or&#xD;
             change in dose of corticosteroids within 2 weeks prior to Screening or during&#xD;
             Screening&#xD;
&#xD;
          -  Use of injectable corticosteroids (including intra-articular corticosteroids) or&#xD;
             intra-articular hyaluronic acid within 4 weeks prior to Screening or during Screening&#xD;
&#xD;
          -  Initiation or change in dose for nonsteroidal anti-inflammatory drugs (NSAIDs)&#xD;
             (including low-dose aspirin and cyclooxygenase-2 inhibitors) within 2 weeks prior to&#xD;
             dosing with the IMP&#xD;
&#xD;
          -  High potency opioid analgesics are prohibited within 2 weeks prior to Screening and&#xD;
             during the trial; other analgesics are allowed (that is, acetaminophen, codeine,&#xD;
             hydrocodone*, propoxyphene*, or tramadol), although not within 24 hours of study&#xD;
             visits with clinical assessments (*not approved in Japan)&#xD;
&#xD;
          -  Current or prior treatment with any of the following:&#xD;
&#xD;
          -  Biologic Disease-modifying anti-rheumatic drugs (DMARDs) (approved or&#xD;
             investigational), including but not limited to:&#xD;
&#xD;
          -  Tumor necrosis factor (TNF) antagonists or biosimilars of these agents (approved or&#xD;
             investigational), or any investigational TNF antagonist&#xD;
&#xD;
          -  Interleukin-6 antagonists&#xD;
&#xD;
          -  Abatacept (CTLA4-Fc)&#xD;
&#xD;
          -  Anakinra* (IL-1 receptor antagonist) (*not approved in Japan)&#xD;
&#xD;
          -  B cell-depleting antibodies (example, rituximab, ocrelizumab*, ofatumumab,&#xD;
             obinutuzumab*, ocaratuzumab*, veltuzumab*, or any biosimilars of these agents&#xD;
             [approved or investigational]) (*not approved in Japan)&#xD;
&#xD;
          -  Anti-BLyS (B lymphocyte stimulator) agents (example, belimumab, tabalumab*) (*not&#xD;
             approved in Japan)&#xD;
&#xD;
          -  Dual BLyS/A proliferation-inducing ligand (APRIL) neutralizing agents (that is,&#xD;
             atacicept*, RCT-18*) (*not approved in Japan)&#xD;
&#xD;
          -  Targeted synthetic DMARDs, specifically:&#xD;
&#xD;
          -  Janus kinase inhibitors&#xD;
&#xD;
          -  Other Bruton's tyrosine kinase (BTK) inhibitors&#xD;
&#xD;
          -  Alkylating agents (example, chlorambucil*, cyclophosphamide) (*not approved in Japan).&#xD;
&#xD;
          -  The following restrictions on nonbiologic DMARD must be followed:&#xD;
&#xD;
          -  Auranofin (Ridaura), minocycline, penicillamine, sulfasalazine, cyclosporine,&#xD;
             mycophenolate (mycophenolate sodium not approved in Japan), tacrolimus, azathioprine:&#xD;
             must have been discontinued for 4 weeks prior to dosing with the IMP&#xD;
&#xD;
          -  Leflunomide (Arava) must have been discontinued 12 weeks prior to dosing with the IMP&#xD;
             if no elimination procedure is followed. Alternately, it should have been discontinued&#xD;
             with the following elimination procedure at least 4 weeks prior to dosing with the&#xD;
             IMP:&#xD;
&#xD;
          -  Cholestyramine at a dosage of 8 gram 3 times a day for at least 24 hours, or activated&#xD;
             charcoal at a dosage of 50 gram 4 times a day for at least 24 hours.&#xD;
&#xD;
          -  Injectable Gold (aurothioglucose* or aurothiomalate): must have been discontinued for&#xD;
             8 weeks prior to dosing with the IMP (*not approved in Japan)&#xD;
&#xD;
          -  Anti-malarials (hydroxychloroquine, chloroquine*) will be allowed in this trial.&#xD;
             Participants may be taking oral hydroxychloroquine (=&lt; 400 mg/day) or chloroquine (=&lt;&#xD;
             250 mg/day), doses must have been stable for at least 12 weeks prior to dosing with&#xD;
             the IMP, and will need to be continued at that stable dose for the duration of the&#xD;
             trial. If discontinued prior to this trial, they must have been discontinued for 4&#xD;
             weeks prior to dosing with the IMP (*not approved in Japan).&#xD;
&#xD;
          -  For MRI Substudy:&#xD;
&#xD;
          -  Inability to comply with MRI scanning, including contraindications to MRI such as&#xD;
             known allergy to gadolinium contrast media, claustrophobia (if the site does not have&#xD;
             ability to scan extremities only), presence of a pacemaker, cochlear implants,&#xD;
             ferromagnetic devices or clips, intracranial vascular clips, insulin pumps, and nerve&#xD;
             stimulators.&#xD;
&#xD;
          -  More than 25% of applicable joints of the target hand and wrist having had prior&#xD;
             surgery or showing maximum Genant-modified Sharp erosion (3.0) or joint-space&#xD;
             narrowing (4.0) scores, based on single posteroanterior radiographs of target hand and&#xD;
             wrist read centrally.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>EMD Serono Research &amp; Development Institute, Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Arizona Arthritis &amp; Rheumatology Associates, P.C.</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis &amp; Rheumatology Research, PLLC</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85037</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>East Bay Rheumatology Medical Group, Inc.</name>
      <address>
        <city>San Leandro</city>
        <state>California</state>
        <zip>94578</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omega Research Consultants</name>
      <address>
        <city>DeBary</city>
        <state>Florida</state>
        <zip>32713</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Research of West Florida, Inc.</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33603</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McIlwain Medical Group, PA</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medication Management, LLC</name>
      <address>
        <city>Greensboro</city>
        <state>North Carolina</state>
        <zip>27410</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Clinic Of Central Texas</name>
      <address>
        <city>San Marcos</city>
        <state>Texas</state>
        <zip>78666</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Italiano de La Plata</name>
      <address>
        <city>La Plata</city>
        <state>Buenos Aires</state>
        <zip>B1900AXI</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Investigaciones Clinicas</name>
      <address>
        <city>Mar del Plata</city>
        <state>Buenos Aires</state>
        <zip>B7600FZ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Medico CER</name>
      <address>
        <city>Quilmes</city>
        <state>Buenos Aires</state>
        <zip>B1878DVB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Investigaciones Clinicas Quilmes</name>
      <address>
        <city>Quilmes</city>
        <state>Buenos Aires</state>
        <zip>B1878GEG</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Privado de Reumatologia</name>
      <address>
        <city>Tucuman</city>
        <state>San Miguel De Tucuman</state>
        <zip>T4000AXL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigaciones Reumatológicas</name>
      <address>
        <city>San Miguel de Tucuman</city>
        <state>Tucuman</state>
        <zip>T4000BRD</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Organizacion Medica de Investigacion (OMI)</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1015ABO</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>APRILLUS</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1046AAQ</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Expertia S.A- Mautalen Salud e Investigación</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1128AAE</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General de Agudos Dr. J. M. Ramos Mejia</name>
      <address>
        <city>Ciudad Autonoma Buenos Aires</city>
        <zip>C1221ADC</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ILAIM-CEOM Inst. Latinoamericano de Inv. Medicas</name>
      <address>
        <city>Cordoba</city>
        <zip>X5000BNB</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto Reumatológico Strusberg</name>
      <address>
        <city>Cordoba</city>
        <zip>X5000EDC</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Polivalente de Asistencia e Inv. Clinica CER</name>
      <address>
        <city>San Juan</city>
        <zip>5400</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MHAT &quot;Hadzhi Dimitar&quot;, OOD</name>
      <address>
        <city>Sliven</city>
        <zip>8800</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>DCC &quot;Alexandrovska&quot;, EOOD</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UMHAT &quot;SofiaMed&quot;, OOD</name>
      <address>
        <city>Sofia</city>
        <zip>1797</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Prosalud</name>
      <address>
        <city>Santiago</city>
        <zip>7500000</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Interin</name>
      <address>
        <city>Santiago</city>
        <zip>7500010</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BioMedica Research Group</name>
      <address>
        <city>Santiago</city>
        <zip>7500710</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Estudios Reumatologicos</name>
      <address>
        <city>Santiago</city>
        <zip>7501126</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Reumatologia y Ortopedia SAS</name>
      <address>
        <city>Barranquilla</city>
        <zip>080001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Riesgo de Fractura S.A.</name>
      <address>
        <city>Bogota</city>
        <zip>110221</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Simedics Ips Sas</name>
      <address>
        <city>Bogotá</city>
        <zip>111211</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion en Reumatologia y Especialidades Medicas SAS. CIREEM</name>
      <address>
        <city>Bogotá</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Servimed S.A.S.</name>
      <address>
        <city>Bucaramanga</city>
        <zip>680003</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica de Artritis Temprana S.A.</name>
      <address>
        <city>Cali</city>
        <zip>76001</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Revmatolog, s.r.o</name>
      <address>
        <city>Jihlava</city>
        <zip>586 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ARTROSCAN s.r.o.</name>
      <address>
        <city>Ostrava - Trebovice</city>
        <zip>722 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CCBR Ostrava s.r.o.</name>
      <address>
        <city>Ostrava</city>
        <zip>702 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CLINTRIAL s.r.o.</name>
      <address>
        <city>Praha 10</city>
        <zip>100 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Thomayerova nemocnice</name>
      <address>
        <city>Praha 4 - Krc</city>
        <zip>140 59</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUDR. Zuzana URBANOVA Revmatologie</name>
      <address>
        <city>Praha 4 Nusle</city>
        <zip>140 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MUDR. Zuzana URBANOVA Revmatologie</name>
      <address>
        <city>Praha 4</city>
        <zip>140 00</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MEDICAL PLUS s.r.o.</name>
      <address>
        <city>Uherske Hradiste</city>
        <zip>686 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>PV-MEDICAL s.r.o.</name>
      <address>
        <city>Zlin</city>
        <zip>760 01</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Investigacion en Artritis y Osteoporosis S.C.</name>
      <address>
        <city>Mexicali</city>
        <state>Baja California Norte</state>
        <zip>21200</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RM Pharma Specialists SA de CV</name>
      <address>
        <city>Mexico</city>
        <state>Distrito Federal</state>
        <zip>03100</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica de Investigacion en Reumatologia y Obesidad S.C.</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44650</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigacion y Biomedicina de Chihuahua, S.C.</name>
      <address>
        <city>Chihuahua</city>
        <zip>31000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion y Atencion Integral Durango CIAID</name>
      <address>
        <city>Durango</city>
        <zip>34270</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ClinicMed Daniluk, Nowak Spółka Jawna</name>
      <address>
        <city>Bialystok</city>
        <zip>15-879</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska lek. Barbara Bazela</name>
      <address>
        <city>Elblag</city>
        <zip>82-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MCBK Iwona Czajkowska Anna Podrażka- Szczepaniak S.C.</name>
      <address>
        <city>Grodzisk Mazowiecki</city>
        <zip>05-825</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Care Clinic</name>
      <address>
        <city>Katowice</city>
        <zip>40-060</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Silmedic sp. z o.o</name>
      <address>
        <city>Katowice</city>
        <zip>40-282</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GLOBE CLINICAL RESEARCH (Globe Badania Kliniczne Sp z o.o.)</name>
      <address>
        <city>Klodzko</city>
        <zip>57-300</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Indywidualna Specjalistyczna Praktyka Lekarska Maciej Zymla</name>
      <address>
        <city>Knurow</city>
        <zip>44-190</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Malopolskie Centrum Medyczne s.c.</name>
      <address>
        <city>Krakow</city>
        <zip>30-510</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grazyna Pulka Specjalistyczny Osrodek &quot;ALL-MED&quot;</name>
      <address>
        <city>Krakow</city>
        <zip>31-024</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Badan Klinicznych S.C.</name>
      <address>
        <city>Poznan</city>
        <zip>60-773</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>RCMed</name>
      <address>
        <city>Sochaczew</city>
        <zip>96-500</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centrum Medyczne AMED</name>
      <address>
        <city>Warsaw</city>
        <zip>03-291</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medycyna Kliniczna</name>
      <address>
        <city>Warszawa</city>
        <zip>00-660</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rheuma Medicus Zaklad Opieki Zdrowotnej</name>
      <address>
        <city>Warszawa</city>
        <zip>02-118</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wojskowy Instytut Medyczny</name>
      <address>
        <city>Warszawa</city>
        <zip>04-141</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Reum-Medica S.C Eliza Roszkowska</name>
      <address>
        <city>Wroclaw</city>
        <zip>50-244</zip>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Research Institute of Emergency Medical Care</name>
      <address>
        <city>St. Petersburg</city>
        <state>Saint Petersburg</state>
        <zip>192242</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Limited Liability Company &quot;Centre of Medical Common Practice&quot;</name>
      <address>
        <city>Novosibirsk</city>
        <zip>630091</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ultramed</name>
      <address>
        <city>Omsk</city>
        <zip>644024</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SPb SBIH &quot;Clinical Rheumatological Hospital # 25&quot;</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>190068</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>LLC Medical Sanitary Unit#157</name>
      <address>
        <city>Saint-Petersburg</city>
        <zip>196066</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NIH &quot;Departmental Hospital on Station Smolensk of OJSC &quot;Russian Railways&quot;</name>
      <address>
        <city>Smolensk</city>
        <zip>214025</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SAIH of Yaroslavl region &quot;Clinical Hospital of Emergency Medical Care n.a. N. V. Solovyev&quot;</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SBHI of Yaroslavl Region &quot;Clinical Hospital # 8&quot;</name>
      <address>
        <city>Yaroslavl</city>
        <zip>150003</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Rheumatology_Site 1</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Military Medical Academy</name>
      <address>
        <city>Belgrade</city>
        <zip>11000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Center Bezanijska kosa</name>
      <address>
        <city>Belgrade</city>
        <zip>11080</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute of Treatment and Rehabilitation &quot;Niska Banja&quot;</name>
      <address>
        <city>Niska Banja</city>
        <zip>18205</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>General Hospital &quot;Dr Laza K. Lazarevic&quot; Sabac</name>
      <address>
        <city>Sabac</city>
        <zip>15000</zip>
        <country>Serbia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wits Clinical Research</name>
      <address>
        <city>Johannesburg</city>
        <state>Gauteng</state>
        <zip>2193</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinresco Centres (Pty) Ltd</name>
      <address>
        <city>Kempton Park</city>
        <state>Gauteng</state>
        <zip>1619</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Emmed Research</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0002</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pretoria Clinical Research Unit</name>
      <address>
        <city>Pretoria</city>
        <state>Gauteng</state>
        <zip>0002</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Naidoo, A</name>
      <address>
        <city>Durban</city>
        <state>KwaZulu-Natal</state>
        <zip>4319</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis Clinical Research Trial Unit</name>
      <address>
        <city>Cape Town</city>
        <state>Western Cape</state>
        <zip>7405</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winelands Medical Research Centre</name>
      <address>
        <city>Stellenbosch</city>
        <state>Western Cape</state>
        <zip>7600</zip>
        <country>South Africa</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Regional CH Dep of Rheumatology SHEI Ivano-Frankivsk NMU</name>
      <address>
        <city>Ivano-Frankivsk</city>
        <zip>76008</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>GI L.T.Malaya Therapy National Institute of the NAMS of Ukraine</name>
      <address>
        <city>Kharkiv</city>
        <zip>61039</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Communal Institution of Healthcare Kharkiv City Clinical Hospital #8</name>
      <address>
        <city>Kharkiv</city>
        <zip>61176</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center Medical Clinic Blagomed LLC</name>
      <address>
        <city>Kyiv</city>
        <zip>01601</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Med Center 'Ok!Clinic+' of International Institute of Clinical Trials LLC</name>
      <address>
        <city>Kyiv</city>
        <zip>02091</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical Center of Revmotsentr LLC</name>
      <address>
        <city>Kyiv</city>
        <zip>04070</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>SI D.F.Chebotariov Institute of Gerontology of NAMSU</name>
      <address>
        <city>Kyiv</city>
        <zip>04114</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CH of State Border Service of Ukraine (Military Base 2522) Dept of Therapy, D.Halytskyi Lviv NMU</name>
      <address>
        <city>Lviv</city>
        <zip>79049</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>M.V. Sklifosovskyi Poltava RCH Dept of Rheumatology HSEIU UMSA</name>
      <address>
        <city>Poltava</city>
        <zip>36011</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A.Novak Transcarpathian Regional Clinical Hospital</name>
      <address>
        <city>Uzhgorod</city>
        <zip>88000</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Pirogov Memorial Medical University</name>
      <address>
        <city>Vinnytsia</city>
        <zip>21018</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI City Hospital #1</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69104</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Zaporizhzhia Regional Clinical Hospital of ZRC</name>
      <address>
        <city>Zaporizhzhia</city>
        <zip>69600</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CI Zaporizhzhia Regional Clinical Hospital of ZRC</name>
      <address>
        <city>Zaporizhzhya</city>
        <zip>69600</zip>
        <country>Ukraine</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Bulgaria</country>
    <country>Chile</country>
    <country>Colombia</country>
    <country>Czechia</country>
    <country>Mexico</country>
    <country>Poland</country>
    <country>Russian Federation</country>
    <country>Serbia</country>
    <country>South Africa</country>
    <country>Ukraine</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Brazil</country>
    <country>Germany</country>
    <country>Hungary</country>
    <country>Romania</country>
    <country>Slovakia</country>
    <country>Spain</country>
  </removed_countries>
  <link>
    <url>https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527-0060</url>
    <description>Trial Awareness and Transparency website</description>
  </link>
  <link>
    <url>https://medical.emdserono.com/en_US/home.html</url>
    <description>US Medical Information website, Medical Resources</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <results_first_submitted>September 4, 2020</results_first_submitted>
  <results_first_submitted_qc>September 4, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">September 28, 2020</results_first_posted>
  <last_update_submitted>September 4, 2020</last_update_submitted>
  <last_update_submitted_qc>September 4, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 28, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Rheumatoid Arthritis</keyword>
  <keyword>American College of Rheumatology</keyword>
  <keyword>High-sensitivity C-reactive protein</keyword>
  <keyword>Bruton's tyrosine kinase</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Arthritis</mesh_term>
    <mesh_term>Arthritis, Rheumatoid</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html</ipd_description>
  </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>July 12, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03233230/Prot_000.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>October 14, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/30/NCT03233230/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>A total of 933 participants with rheumatoid arthritis were screened. Out of which, 390 participants were randomized in ratio of 1:1:1:1 to 1 of the 4 treatment groups: Placebo; M2951 25 milligrams (mg) once daily (QD), M2951 75 mg QD and M2951 50 mg twice daily (BID).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
        </group>
        <group group_id="P2">
          <title>M2951 25 mg QD</title>
          <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
        </group>
        <group group_id="P3">
          <title>M2951 75 mg QD</title>
          <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
        </group>
        <group group_id="P4">
          <title>M2951 50 mg BID</title>
          <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="98"/>
                <participants group_id="P3" count="96"/>
                <participants group_id="P4" count="99"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="82"/>
                <participants group_id="P2" count="83"/>
                <participants group_id="P3" count="84"/>
                <participants group_id="P4" count="91"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="15"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="12"/>
                <participants group_id="P4" count="8"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Efficacy</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_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Other</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="5"/>
                <participants group_id="P3" count="5"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The modified intent-to-treat (mITT) analysis set included all randomized participants who received at least one dose of Investigational Medicinal Product (IMP) (M2951 or placebo).</population>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
        </group>
        <group group_id="B2">
          <title>M2951 25 mg QD</title>
          <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
        </group>
        <group group_id="B3">
          <title>M2951 75 mg QD</title>
          <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
        </group>
        <group group_id="B4">
          <title>M2951 50 mg BID</title>
          <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
        </group>
        <group group_id="B5">
          <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="97"/>
            <count group_id="B2" value="98"/>
            <count group_id="B3" value="96"/>
            <count group_id="B4" value="99"/>
            <count group_id="B5" value="390"/>
          </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="52.9" spread="12.24"/>
                    <measurement group_id="B2" value="50.9" spread="13.15"/>
                    <measurement group_id="B3" value="53.3" spread="11.33"/>
                    <measurement group_id="B4" value="53.7" spread="12.13"/>
                    <measurement group_id="B5" value="52.7" spread="12.21"/>
                  </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="77"/>
                    <measurement group_id="B2" value="82"/>
                    <measurement group_id="B3" value="76"/>
                    <measurement group_id="B4" value="77"/>
                    <measurement group_id="B5" value="312"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="20"/>
                    <measurement group_id="B4" value="22"/>
                    <measurement group_id="B5" value="78"/>
                  </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="32"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="35"/>
                    <measurement group_id="B4" value="38"/>
                    <measurement group_id="B5" value="138"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="65"/>
                    <measurement group_id="B2" value="65"/>
                    <measurement group_id="B3" value="61"/>
                    <measurement group_id="B4" value="61"/>
                    <measurement group_id="B5" value="252"/>
                  </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_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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                    <measurement group_id="B5" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="92"/>
                    <measurement group_id="B2" value="94"/>
                    <measurement group_id="B3" value="91"/>
                    <measurement group_id="B4" value="97"/>
                    <measurement group_id="B5" value="374"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                    <measurement group_id="B4" value="2"/>
                    <measurement group_id="B5" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
        <description>ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants * 100.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of Investigational Medicinal Product (IMP) (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
          <description>ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants * 100.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of Investigational Medicinal Product (IMP) (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="49.5"/>
                    <measurement group_id="O2" value="59.2"/>
                    <measurement group_id="O3" value="51.0"/>
                    <measurement group_id="O4" value="59.6"/>
                  </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>0.1746</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.48</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.84</ci_lower_limit>
            <ci_upper_limit>2.61</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>0.8283</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.61</ci_lower_limit>
            <ci_upper_limit>1.87</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>0.1298</p_value>
            <method>Regression, Logistic</method>
            <param_type>Odds Ratio (OR)</param_type>
            <param_value>1.55</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.88</ci_lower_limit>
            <ci_upper_limit>2.74</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [&lt;] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
        <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 &lt; 3.2 based on DAS28- hsCRP at Week 12 were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [&lt;] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
          <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 &lt; 3.2 based on DAS28- hsCRP at Week 12 were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.2"/>
                    <measurement group_id="O2" value="20.4"/>
                    <measurement group_id="O3" value="24.0"/>
                    <measurement group_id="O4" value="20.2"/>
                  </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>0.0077</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.04</ci_lower_limit>
            <ci_upper_limit>0.23</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>0.0013</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.17</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.07</ci_lower_limit>
            <ci_upper_limit>0.27</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>0.0080</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.13</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.04</ci_lower_limit>
            <ci_upper_limit>0.23</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [&lt;] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
        <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (&lt;) 2.6 indicated clinical remission. Percentage of participants with low DAS28 &lt; 2.6 based on DAS28- hsCRP at Week 12 were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [&lt;] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
          <description>Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (&lt;) 2.6 indicated clinical remission. Percentage of participants with low DAS28 &lt; 2.6 based on DAS28- hsCRP at Week 12 were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                    <measurement group_id="O2" value="10.2"/>
                    <measurement group_id="O3" value="10.4"/>
                    <measurement group_id="O4" value="10.1"/>
                  </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>0.0056</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.03</ci_lower_limit>
            <ci_upper_limit>0.17</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>0.0050</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.03</ci_lower_limit>
            <ci_upper_limit>0.17</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>0.0053</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.03</ci_lower_limit>
            <ci_upper_limit>0.17</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)</title>
        <description>ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants * 100.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)</title>
          <description>ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants * 100.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.6"/>
                    <measurement group_id="O2" value="28.6"/>
                    <measurement group_id="O3" value="27.1"/>
                    <measurement group_id="O4" value="26.3"/>
                  </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>0.1419</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.09</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.21</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>0.2202</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.07</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>0.19</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>0.2328</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.07</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>0.19</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)</title>
        <description>ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants * 100.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)</title>
          <description>ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants * 100.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.2"/>
                    <measurement group_id="O2" value="11.2"/>
                    <measurement group_id="O3" value="10.4"/>
                    <measurement group_id="O4" value="10.1"/>
                  </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>0.1232</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.06</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.02</ci_lower_limit>
            <ci_upper_limit>0.15</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>0.1725</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.14</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>0.1795</p_value>
            <method>Cochran-Mantel-Haenszel</method>
            <param_type>Response rate difference</param_type>
            <param_value>0.05</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.13</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</title>
        <description>Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
        <time_frame>up to Week 16</time_frame>
        <population>The safety analysis set (SAF) included all participants who received at least 1 dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</title>
          <description>Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.</description>
          <population>The safety analysis set (SAF) included all participants who received at least 1 dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TEAEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44"/>
                    <measurement group_id="O2" value="48"/>
                    <measurement group_id="O3" value="48"/>
                    <measurement group_id="O4" value="50"/>
                  </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="2"/>
                    <measurement group_id="O3" value="2"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</title>
        <description>Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.</description>
        <time_frame>up to Week 16</time_frame>
        <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)</title>
          <description>Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.</description>
          <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Grade 1</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="33"/>
                    <measurement group_id="O2" value="42"/>
                    <measurement group_id="O3" value="37"/>
                    <measurement group_id="O4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 2</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="23"/>
                    <measurement group_id="O4" value="17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="1"/>
                    <measurement group_id="O4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 4</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="0"/>
                    <measurement group_id="O4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Grade 5</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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</title>
        <description>Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.</description>
        <time_frame>up to Week 16</time_frame>
        <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Change From Baseline in Vital Signs</title>
          <description>Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.</description>
          <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters</title>
        <description>Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.</description>
        <time_frame>up to Week 16</time_frame>
        <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters</title>
          <description>Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.</description>
          <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings</title>
        <description>12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.</description>
        <time_frame>up to Week 16</time_frame>
        <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings</title>
          <description>12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.</description>
          <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16</title>
        <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
        <time_frame>Baseline, Week 2, 4, 8, 12 and 16</time_frame>
        <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16</title>
          <description>Change in the serum levels of IgG, IgA, IgM were assessed.</description>
          <population>The SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). 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 (g/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="96"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IgG: Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="96"/>
                    <count group_id="O3" value="95"/>
                    <count group_id="O4" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="1.083"/>
                    <measurement group_id="O2" value="-0.07" spread="1.042"/>
                    <measurement group_id="O3" value="-0.21" spread="0.968"/>
                    <measurement group_id="O4" value="-0.09" spread="1.062"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgG: Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="93"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="1.465"/>
                    <measurement group_id="O2" value="-0.15" spread="1.576"/>
                    <measurement group_id="O3" value="-0.34" spread="1.254"/>
                    <measurement group_id="O4" value="-0.17" spread="1.168"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgG: Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="90"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="87"/>
                    <count group_id="O4" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.12" spread="1.513"/>
                    <measurement group_id="O2" value="-0.28" spread="2.052"/>
                    <measurement group_id="O3" value="-0.37" spread="1.565"/>
                    <measurement group_id="O4" value="-0.35" spread="2.037"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgG: Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="89"/>
                    <count group_id="O3" value="81"/>
                    <count group_id="O4" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.47" spread="1.617"/>
                    <measurement group_id="O2" value="-0.17" spread="2.080"/>
                    <measurement group_id="O3" value="-0.33" spread="1.493"/>
                    <measurement group_id="O4" value="-0.23" spread="1.781"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgG: Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="60"/>
                    <count group_id="O3" value="63"/>
                    <count group_id="O4" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.08" spread="1.829"/>
                    <measurement group_id="O2" value="-0.14" spread="2.349"/>
                    <measurement group_id="O3" value="-0.14" spread="1.808"/>
                    <measurement group_id="O4" value="0.06" spread="1.960"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgA: Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="96"/>
                    <count group_id="O3" value="95"/>
                    <count group_id="O4" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.253"/>
                    <measurement group_id="O2" value="-0.15" spread="1.187"/>
                    <measurement group_id="O3" value="0.00" spread="0.242"/>
                    <measurement group_id="O4" value="0.03" spread="0.369"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgA: Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="93"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" spread="0.326"/>
                    <measurement group_id="O2" value="-0.01" spread="0.359"/>
                    <measurement group_id="O3" value="-0.05" spread="0.333"/>
                    <measurement group_id="O4" value="0.02" spread="0.396"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgA: Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="90"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="87"/>
                    <count group_id="O4" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.02" spread="0.346"/>
                    <measurement group_id="O2" value="-0.16" spread="1.322"/>
                    <measurement group_id="O3" value="-0.06" spread="0.373"/>
                    <measurement group_id="O4" value="0.07" spread="0.567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgA: Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="89"/>
                    <count group_id="O3" value="81"/>
                    <count group_id="O4" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.02" spread="0.373"/>
                    <measurement group_id="O2" value="0.01" spread="0.444"/>
                    <measurement group_id="O3" value="-0.08" spread="0.388"/>
                    <measurement group_id="O4" value="0.05" spread="0.545"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgA: Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="60"/>
                    <count group_id="O3" value="63"/>
                    <count group_id="O4" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.01" spread="0.466"/>
                    <measurement group_id="O2" value="0.07" spread="0.465"/>
                    <measurement group_id="O3" value="-0.11" spread="0.380"/>
                    <measurement group_id="O4" value="0.05" spread="0.478"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgM: Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="95"/>
                    <count group_id="O2" value="96"/>
                    <count group_id="O3" value="95"/>
                    <count group_id="O4" value="99"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.198"/>
                    <measurement group_id="O2" value="-0.04" spread="0.183"/>
                    <measurement group_id="O3" value="-0.03" spread="0.281"/>
                    <measurement group_id="O4" value="-0.01" spread="0.323"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgM: Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="94"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="93"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04" spread="0.199"/>
                    <measurement group_id="O2" value="-0.11" spread="0.224"/>
                    <measurement group_id="O3" value="-0.11" spread="0.217"/>
                    <measurement group_id="O4" value="-0.05" spread="0.385"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgM: Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="90"/>
                    <count group_id="O2" value="94"/>
                    <count group_id="O3" value="87"/>
                    <count group_id="O4" value="95"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.03" spread="0.310"/>
                    <measurement group_id="O2" value="-0.20" spread="0.243"/>
                    <measurement group_id="O3" value="-0.23" spread="0.327"/>
                    <measurement group_id="O4" value="-0.10" spread="0.485"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgM: Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="83"/>
                    <count group_id="O2" value="89"/>
                    <count group_id="O3" value="81"/>
                    <count group_id="O4" value="88"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.01" spread="0.265"/>
                    <measurement group_id="O2" value="-0.20" spread="0.309"/>
                    <measurement group_id="O3" value="-0.25" spread="0.296"/>
                    <measurement group_id="O4" value="-0.17" spread="0.406"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IgM: Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="60"/>
                    <count group_id="O2" value="60"/>
                    <count group_id="O3" value="63"/>
                    <count group_id="O4" value="67"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="0.776"/>
                    <measurement group_id="O2" value="-0.12" spread="0.436"/>
                    <measurement group_id="O3" value="-0.22" spread="0.246"/>
                    <measurement group_id="O4" value="-0.12" spread="0.487"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16</title>
        <description>Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.</description>
        <time_frame>Baseline, Week 2, 4, 8, 12 and 16</time_frame>
        <population>SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed specifies 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 point.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16</title>
          <description>Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.</description>
          <population>SAF included all participants who received at least 1 dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed specifies 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 point.</population>
          <units>cells per microliter (cells/microliter)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="90"/>
                <count group_id="O2" value="90"/>
                <count group_id="O3" value="92"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="87"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="92"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13" spread="111.0"/>
                    <measurement group_id="O2" value="264" spread="1832.7"/>
                    <measurement group_id="O3" value="161" spread="648.3"/>
                    <measurement group_id="O4" value="74" spread="144.8"/>
                  </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="90"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="91"/>
                    <count group_id="O4" value="93"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20" spread="115.7"/>
                    <measurement group_id="O2" value="71" spread="130.1"/>
                    <measurement group_id="O3" value="66" spread="145.3"/>
                    <measurement group_id="O4" value="93" spread="137.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="81"/>
                    <count group_id="O2" value="90"/>
                    <count group_id="O3" value="82"/>
                    <count group_id="O4" value="91"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21" spread="87.5"/>
                    <measurement group_id="O2" value="35" spread="103.1"/>
                    <measurement group_id="O3" value="56" spread="188.1"/>
                    <measurement group_id="O4" value="59" spread="145.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="82"/>
                    <count group_id="O2" value="85"/>
                    <count group_id="O3" value="77"/>
                    <count group_id="O4" value="83"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-22" spread="136.4"/>
                    <measurement group_id="O2" value="41" spread="111.8"/>
                    <measurement group_id="O3" value="51" spread="156.2"/>
                    <measurement group_id="O4" value="54" spread="145.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="56"/>
                    <count group_id="O2" value="58"/>
                    <count group_id="O3" value="60"/>
                    <count group_id="O4" value="64"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20" spread="121.9"/>
                    <measurement group_id="O2" value="-3" spread="108.5"/>
                    <measurement group_id="O3" value="-40" spread="133.5"/>
                    <measurement group_id="O4" value="-19" spread="235.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12</title>
        <description>ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter [mg/dL]), and participant's global assessment (visual analog scale [VAS]: 0 centimeter (cm) [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were less than or equal to (&lt;=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12</title>
          <description>ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter [mg/dL]), and participant's global assessment (visual analog scale [VAS]: 0 centimeter (cm) [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were less than or equal to (&lt;=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="0.0"/>
                    <measurement group_id="O3" value="1.0"/>
                    <measurement group_id="O4" value="3.0"/>
                  </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>
            <param_type>Response rate difference</param_type>
            <param_value>0.00</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.04</ci_lower_limit>
            <ci_upper_limit>0.04</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.01</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.06</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.01</ci_lower_limit>
            <ci_upper_limit>0.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=&lt;] 2.8 at Week 12</title>
        <description>CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =&lt; 2.8 indicated clinical remission. Percentage of participants with CDAI score =&lt; 2.8 were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=&lt;] 2.8 at Week 12</title>
          <description>CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =&lt; 2.8 indicated clinical remission. Percentage of participants with CDAI score =&lt; 2.8 were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0"/>
                    <measurement group_id="O2" value="4.1"/>
                    <measurement group_id="O3" value="6.3"/>
                    <measurement group_id="O4" value="3.0"/>
                  </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>
            <param_type>Response rate difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.02</ci_lower_limit>
            <ci_upper_limit>0.09</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.05</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>0.12</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.02</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.08</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=&lt;] 3.3 at Week 12</title>
        <description>SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =&lt; 3.3 indicated clinical remission. Percentage of participants with SDAI score =&lt; 3.3 at Week 12 were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=&lt;] 3.3 at Week 12</title>
          <description>SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =&lt; 3.3 indicated clinical remission. Percentage of participants with SDAI score =&lt; 3.3 at Week 12 were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0"/>
                    <measurement group_id="O2" value="3.1"/>
                    <measurement group_id="O3" value="4.2"/>
                    <measurement group_id="O4" value="3.0"/>
                  </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>
            <param_type>Response rate difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.01</ci_lower_limit>
            <ci_upper_limit>0.09</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.04</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>0.10</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.03</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.01</ci_lower_limit>
            <ci_upper_limit>0.09</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12</title>
        <description>EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP &gt;5.1, low disease activity: DAS28-CRP &lt;3.2, and remission: DAS28-CRP &lt;2.6. EULAR DAS28-CRP responder index: good (absolute: &lt;3.2 or &gt;1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: &gt;5.1 or &lt;0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.</description>
        <time_frame>Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12</title>
          <description>EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP &gt;5.1, low disease activity: DAS28-CRP &lt;3.2, and remission: DAS28-CRP &lt;2.6. EULAR DAS28-CRP responder index: good (absolute: &lt;3.2 or &gt;1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: &gt;5.1 or &lt;0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo).</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="97"/>
                <count group_id="O2" value="98"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="54.6"/>
                    <measurement group_id="O2" value="65.3"/>
                    <measurement group_id="O3" value="66.7"/>
                    <measurement group_id="O4" value="71.7"/>
                  </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>
            <param_type>Response rate difference</param_type>
            <param_value>0.11</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.03</ci_lower_limit>
            <ci_upper_limit>0.24</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.12</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.02</ci_lower_limit>
            <ci_upper_limit>0.25</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>
            <param_type>Response rate difference</param_type>
            <param_value>0.18</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>0.31</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)</title>
        <description>The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire [HAQ], and C-reactive protein [CRP]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)</title>
          <description>The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire [HAQ], and C-reactive protein [CRP]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.51" spread="25.779"/>
                    <measurement group_id="O2" value="34.66" spread="29.033"/>
                    <measurement group_id="O3" value="33.09" spread="27.724"/>
                    <measurement group_id="O4" value="36.99" spread="26.241"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
        <description>DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter [mg/L]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP &lt; 3.2 implied low disease activity and &gt;= 3.2 to &lt;= 5.1 implied moderate disease activity, &gt; 5.1 implied high disease activity. DAS28-hsCRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(hsCRP in mg/L +1) + 0.014* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12</title>
          <description>DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter [mg/L]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP &lt; 3.2 implied low disease activity and &gt;= 3.2 to &lt;= 5.1 implied moderate disease activity, &gt; 5.1 implied high disease activity. DAS28-hsCRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(hsCRP in mg/L +1) + 0.014* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.21" spread="1.048"/>
                    <measurement group_id="O2" value="-1.45" spread="1.230"/>
                    <measurement group_id="O3" value="-1.62" spread="1.257"/>
                    <measurement group_id="O4" value="-1.75" spread="1.229"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12</title>
        <description>The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12</title>
          <description>The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16.9" spread="13.09"/>
                    <measurement group_id="O2" value="-18.0" spread="13.00"/>
                    <measurement group_id="O3" value="-18.9" spread="14.33"/>
                    <measurement group_id="O4" value="-20.3" spread="13.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12</title>
        <description>SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12</title>
          <description>SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.000" spread="13.5175"/>
                    <measurement group_id="O2" value="-18.647" spread="13.5957"/>
                    <measurement group_id="O3" value="-19.404" spread="14.1591"/>
                    <measurement group_id="O4" value="-21.053" spread="14.3720"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</title>
        <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</title>
          <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>joints</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TJC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11" spread="12.0"/>
                    <measurement group_id="O2" value="-11" spread="10.6"/>
                    <measurement group_id="O3" value="-13" spread="13.2"/>
                    <measurement group_id="O4" value="-12" spread="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SJC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-7" spread="7.5"/>
                    <measurement group_id="O2" value="-8" spread="6.1"/>
                    <measurement group_id="O3" value="-8" spread="7.7"/>
                    <measurement group_id="O4" value="-8" spread="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>millimeter (mm)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20" spread="29.6"/>
                    <measurement group_id="O2" value="-19" spread="27.9"/>
                    <measurement group_id="O3" value="-17" spread="29.6"/>
                    <measurement group_id="O4" value="-25" spread="25.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>millimeter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21" spread="24.7"/>
                    <measurement group_id="O2" value="-24" spread="26.9"/>
                    <measurement group_id="O3" value="-22" spread="24.7"/>
                    <measurement group_id="O4" value="-25" spread="26.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</title>
        <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</title>
          <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.38" spread="0.567"/>
                    <measurement group_id="O2" value="-0.58" spread="0.662"/>
                    <measurement group_id="O3" value="-0.40" spread="0.658"/>
                    <measurement group_id="O4" value="-0.52" spread="0.616"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>millimeter</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-29" spread="21.2"/>
                    <measurement group_id="O2" value="-33" spread="26.5"/>
                    <measurement group_id="O3" value="-34" spread="26.1"/>
                    <measurement group_id="O4" value="-37" spread="25.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
        <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
          <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>milligram per liter (mg/L)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.11" spread="25.925"/>
                    <measurement group_id="O2" value="-6.42" spread="23.280"/>
                    <measurement group_id="O3" value="-5.45" spread="28.807"/>
                    <measurement group_id="O4" value="-7.69" spread="23.007"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</title>
        <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12</title>
          <description>Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>TJC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-39" spread="45.6"/>
                    <measurement group_id="O2" value="-46" spread="44.2"/>
                    <measurement group_id="O3" value="-51" spread="42.8"/>
                    <measurement group_id="O4" value="-49" spread="37.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>SJC</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-46" spread="52.7"/>
                    <measurement group_id="O2" value="-53" spread="42.6"/>
                    <measurement group_id="O3" value="-56" spread="40.3"/>
                    <measurement group_id="O4" value="-58" spread="43.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="96"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-13" spread="111.0"/>
                    <measurement group_id="O2" value="-21" spread="69.3"/>
                    <measurement group_id="O3" value="-13" spread="65.7"/>
                    <measurement group_id="O4" value="-33" spread="35.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23" spread="65.0"/>
                    <measurement group_id="O2" value="-32" spread="38.4"/>
                    <measurement group_id="O3" value="-29" spread="40.5"/>
                    <measurement group_id="O4" value="-32" spread="48.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</title>
        <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12</title>
          <description>HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="95"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="95"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-20.09" spread="40.084"/>
                    <measurement group_id="O2" value="-31.85" spread="37.124"/>
                    <measurement group_id="O3" value="-21.27" spread="44.571"/>
                    <measurement group_id="O4" value="-27.12" spread="42.624"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</title>
        <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12</title>
          <description>The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="98"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-42" spread="31.4"/>
                    <measurement group_id="O2" value="-44" spread="51.9"/>
                    <measurement group_id="O3" value="-47" spread="34.9"/>
                    <measurement group_id="O4" value="-52" spread="33.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
        <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12</title>
          <description>hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.</description>
          <population>The mITT analysis set included all randomized participants who received at least one dose of IMP (M2951 or placebo). Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="97"/>
                <count group_id="O3" value="96"/>
                <count group_id="O4" value="99"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95.01" spread="380.161"/>
                    <measurement group_id="O2" value="10.93" spread="167.257"/>
                    <measurement group_id="O3" value="182.57" spread="1775.154"/>
                    <measurement group_id="O4" value="-13.91" spread="105.688"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</title>
        <description>A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The Magnetic Resonance Imaging (MRI) analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</title>
          <description>A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.</description>
          <population>The Magnetic Resonance Imaging (MRI) analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="49"/>
                <count group_id="O3" value="47"/>
                <count group_id="O4" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="1.9"/>
                    <measurement group_id="O2" value="-1" spread="2.5"/>
                    <measurement group_id="O3" value="-1" spread="3.4"/>
                    <measurement group_id="O4" value="-1" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</title>
        <description>A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>The MRI analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12</title>
          <description>A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.</description>
          <population>The MRI analysis set included all randomized participants who have at least at least 1 pre-dose and 1 post-dose MRI assessment. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="49"/>
                <count group_id="O3" value="47"/>
                <count group_id="O4" value="51"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1" spread="5.8"/>
                    <measurement group_id="O2" value="0" spread="4.6"/>
                    <measurement group_id="O3" value="0" spread="5.4"/>
                    <measurement group_id="O4" value="0" spread="4.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</title>
        <description>The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>Quality of Life (QoL) Analysis Set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. &quot;Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12</title>
          <description>The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.</description>
          <population>Quality of Life (QoL) Analysis Set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. &quot;Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="87"/>
                <count group_id="O2" value="93"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.41" spread="0.543"/>
                    <measurement group_id="O2" value="-0.61" spread="0.637"/>
                    <measurement group_id="O3" value="-0.45" spread="0.657"/>
                    <measurement group_id="O4" value="-0.53" spread="0.631"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12</title>
        <description>The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>QoL analysis set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12</title>
          <description>The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).</description>
          <population>QoL analysis set: all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post baseline QoL assessment. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="87"/>
                <count group_id="O2" value="93"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>PCS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" spread="7.10"/>
                    <measurement group_id="O2" value="7.1" spread="8.50"/>
                    <measurement group_id="O3" value="6.4" spread="8.50"/>
                    <measurement group_id="O4" value="7.1" spread="8.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>MCS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.9" spread="11.46"/>
                    <measurement group_id="O2" value="5.7" spread="8.41"/>
                    <measurement group_id="O3" value="5.0" spread="11.72"/>
                    <measurement group_id="O4" value="4.7" spread="8.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12</title>
        <description>The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.</description>
        <time_frame>Baseline, Week 12</time_frame>
        <population>QoL analysis set included all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post Baseline QoL assessment. Here, &quot;Overall 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 M2951 orally for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>M2951 25 mg QD</title>
            <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
          </group>
          <group group_id="O3">
            <title>M2951 75 mg QD</title>
            <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
          </group>
          <group group_id="O4">
            <title>M2951 50 mg BID</title>
            <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12</title>
          <description>The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.</description>
          <population>QoL analysis set included all randomized participants who have received at least 1 dose of IMP (M2951 or placebo) and had at least 1 Baseline and 1 post Baseline QoL assessment. Here, &quot;Overall Number of Participants Analyzed&quot; signifies those participants who were evaluable for this outcome measure.</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="87"/>
                <count group_id="O2" value="93"/>
                <count group_id="O3" value="86"/>
                <count group_id="O4" value="92"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9" spread="11.4"/>
                    <measurement group_id="O2" value="10" spread="9.4"/>
                    <measurement group_id="O3" value="9" spread="9.0"/>
                    <measurement group_id="O4" value="8" spread="10.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>up to Week 16</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants received placebo matched to M2951 orally for 12 weeks.</description>
        </group>
        <group group_id="E2">
          <title>M2951 25 mg QD</title>
          <description>Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.</description>
        </group>
        <group group_id="E3">
          <title>M2951 75 mg QD</title>
          <description>Participants received 75 mg of M2951 orally QD for 12 weeks.</description>
        </group>
        <group group_id="E4">
          <title>M2951 50 mg BID</title>
          <description>Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA version 22.0</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="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Hepatotoxicity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Hypersensitivity</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Osteomyelitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Tibia fracture</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Chronic obstructive pulmonary disease</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphoedema</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
              <event>
                <sub_title>Thrombophlebitis superficial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA version 22.0</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="11" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="13" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="8" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="7" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dyslipidaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="99"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="97"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="98"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="96"/>
                <counts group_id="E4" subjects_affected="8" subjects_at_risk="99"/>
              </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>
    </certain_agreements>
    <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/NCT03233230
org study id: MS200527-0060
secondary id: 2017-000384-32
nct id: NCT03233230
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study was to determine the efficacy, dose response, and safety of M52951
      in participants with Rheumatoid Arthritis (RA), and to consider a dose to took forward into
      Phase III development.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Percentage of Participants Who Achieved American College of Rheumatology 20 Percent (%) Response Criteria (ACR20) Assessed Using High-Sensitivity C-reactive Protein (hsCRP) at Week 12
time frame: Week 12
description: ACR20 response: a participant has at least 20% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 20% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire-Disability Index (HAQ-DI); and 5) acute phase reactant as measured by high-sensitivity C-reactive protein (hsCRP). Percentage of participants with ACR20 response using hsCRP = Number of participants with ACR20 response using hsCRP divided by total modified intent-to-treat (mITT) participants * 100.
measure: Percentage of Participants With Low Disease Activity Score (DAS28 Less Than [<] 3.2) Based on 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
time frame: Week 12
description: Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. Percentage of participants with low DAS28 < 3.2 based on DAS28- hsCRP at Week 12 were reported.
measure: Percentage of Participants With Remission Disease Activity Score (DAS28 Less Than [<] 2.6) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
time frame: Week 12
description: Disease Activity Score (DAS) based on a 28 joint count hsCRP consisted of composite numerical score of following variables: tender joint count (TJC28), swollen joint count (SJC28), hsCRP (mg/mL), and participant's global assessment of disease activity. DAS28-hsCRP was calculated using following formula: DAS28-hsCRP equals to (=) 0.56*square root (sqrt) (TJC28) plus (+) 0.28*sqrt (SJC28) + 0.36*natural log(hsCRP+1) + 0.014* participant's global assessment of disease activity + 0.96. Scores ranged 0-9.4, where lower scores indicated less disease activity. A DAS28 score less than (<) 2.6 indicated clinical remission. Percentage of participants with low DAS28 < 2.6 based on DAS28- hsCRP at Week 12 were reported.
measure: Percentage of Participants Achieving American College of Rheumatology 50% Response Criteria (ACR50)
time frame: Week 12
description: ACR50 response: a participant has at least 50% improvement in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 50% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR50 response = Number of participants with ACR50 response divided by total mITT participants * 100.
measure: Percentage of Participants Achieving American College of Rheumatology 70% Response Criteria (ACR70)
time frame: Week 12
description: ACR70 response: a participant has at least 70% improvement ACR70 response in both tender joint counts (based on a total of 68 joints) and swollen joint counts (based on a total of 66 joints) together with 70% improvement in at least 3 of the following: 1) participant's assessment of pain; 2) participant's global assessment of disease activity; 3) physician's global assessment of disease activity; 4) participant's assessment of physical function measured by Health Assessment Questionnaire - Disability Index [HAQ-DI]; and 5) acute phase reactant as measured by High-sensitivity C-reactive protein [hsCRP]. Percentage of participants with ACR70 response = Number of participants with ACR70 response divided by total mITT participants * 100.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
time frame: up to Week 16
description: Adverse event (AE) was defined as any untoward medical occurrence in a participant, which does not necessarily have causal relationship with treatment. A serious AE was defined as an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inparticipant hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs: events between first dose of study drug that were absent before treatment/that worsened relative to pre-treatment state up to 16 weeks. TEAEs included both serious TEAEs and non-serious TEAEs. Number of participants with TEAEs and serious TEAEs were reported.
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) by Severity According to National Cancer Institute-Common Terminology Criteria for Adverse Events Version 4.03 (NCI-CTCAE v4.03)
time frame: up to Week 16
description: Severity of TEAEs were graded using NCI-CTCAE v4.03 toxicity grades, as follows: Grade 1= Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening and Grade 5 = Death. Number of participants with TEAEs by severity were reported.
measure: Number of Participants With Clinically Significant Change From Baseline in Vital Signs
time frame: up to Week 16
description: Vital signs included body temperature, systolic and diastolic blood pressure, pulse rate, respiratory rate, weight and height. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in vital signs were reported.
measure: Number of Participants With Clinically Significant Changes From Baseline in Laboratory Parameters
time frame: up to Week 16
description: Laboratory investigation included hematology, biochemistry, urinalysis and coagulation. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in laboratory parameters were reported.
measure: Number of Participants With Clinically Significant Changes From Baseline in 12-Lead Electrocardiogram (ECG) Findings
time frame: up to Week 16
description: 12-lead ECG recordings included rhythm, heart rate (as measured by RR interval), PR interval, QRS duration, and QT interval. The corrected QT interval (QTcF) was calculated using Fridericia's formula. 12-lead ECG recordings were obtained after the participants have rested for at least 10 minutes in semisupine position. Clinical significance was determined by the investigator. The number of participants with clinically significant changes from baseline in 12-lead ECG findings were reported.
measure: Change From Baseline in Serum Immunoglobulin (Ig) Levels (IgG, IgA, IgM) at Week 2, 4, 8, 12 and 16
time frame: Baseline, Week 2, 4, 8, 12 and 16
description: Change in the serum levels of IgG, IgA, IgM were assessed.
measure: Change From Baseline in B Cell Count at Week 2, 4, 8, 12 and 16
time frame: Baseline, Week 2, 4, 8, 12 and 16
description: Flow cytometry analysis of lymphocyte populations using four-color fluorescence-activated cell sorting was performed for the analysis of B cell counts.
measure: Percentage of Participants With Remission Assessed by American College of Rheumatology-European League Against Rheumatism (ACR-EULAR) Boolean at Week 12
time frame: Week 12
description: ACR-EULAR Boolean remission was when a participant satisfied all of the following: tender joint count, swollen joint count (both based on a 28-joint assessment), C-reactive Protein (in milligrams per deciliter [mg/dL]), and participant's global assessment (visual analog scale [VAS]: 0 centimeter (cm) [very well] to 10 cm [worst], higher scores indicated worse health condition) and all scores were less than or equal to (<=) 1. Percentage of participants with ACR-EULAR Boolean Remission were reported.
measure: Percentage of Participants With Clinical Disease Activity Index (CDAI) Score Less Than or Equal to [=<] 2.8 at Week 12
time frame: Week 12
description: CDAI: a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity). CDAI score =< 2.8 indicated clinical remission. Percentage of participants with CDAI score =< 2.8 were reported.
measure: Percentage of Participants With Simplified Disease Activity Index (SDAI) Score Less Than or Equal to [=<] 3.3 at Week 12
time frame: Week 12
description: SDAI was calculated based on following formula: SDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the Disease Activity Score [DAS] (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity). SDAI score =< 3.3 indicated clinical remission. Percentage of participants with SDAI score =< 3.3 at Week 12 were reported.
measure: Percentage of Participants With Good or Moderate European League Against Rheumatism (EULAR) Responses at Week 12
time frame: Week 12
description: EULAR Responder index based on 28 joint counts categorizes clinical response based on improvement since baseline in DAS28-CRP. DAS28-CRP scores range from 0-9.4, where lower scores indicated less disease activity. High disease activity: DAS28-CRP >5.1, low disease activity: DAS28-CRP <3.2, and remission: DAS28-CRP <2.6. EULAR DAS28-CRP responder index: good (absolute: <3.2 or >1.2 improvement from baseline), moderate (absolute: 3.2-5.1 or 0.6-1.2 improvement from baseline), or no response (absolute: >5.1 or <0.6 improvement from baseline). Percentage of Participants With Good or Moderate EULAR Responses were reported.
measure: American College of Rheumatology (ACR) Hybrid Scores Computed Using High-Sensitivity C-reactive Protein (hsCRP)
time frame: Baseline, Week 12
description: The hybrid ACR combines the ACR 20/50/70 response with the mean percent change in all 7 ACR core components, thus providing a percent improvement from baseline on a continuous scale. For each participant, the mean percent improvement from baseline across the 7 ACR core set measures (tender joint count, swollen joint count, Patient's Global Assessment of Disease Activity, Physician's Global Assessment of Disease Activity, disability index of the Health Assessment Questionnaire [HAQ], and C-reactive protein [CRP]) was calculated (a positive change indicated improvement, and the maximum worst change was limited to -100%) and the ACR20, ACR50, and ACR70 response is determined. The hybrid ACR is determined from a reference table taking into account both ACR response and mean percent improvement in the core set measures. Scores can range from -100% (maximal worsening) to 100% (maximal improvement).
measure: Change From Baseline in Disease Activity Score (DAS) Based on a 28 Joint Count-High-Sensitivity C-reactive Protein (DAS28-hsCRP) at Week 12
time frame: Baseline, Week 12
description: DAS28 was a composite score used for measuring disease activity in participants with rheumatoid arthritis. The calculation was based on the tender joint count (out of 28 joints), swollen joint count (out of 28 joints), hsCRP (milligrams per liter [mg/L]) and Participant's Global Assessment of Disease Activity. Total DAS28-hsCRP score ranged from 0 (none) to 9.4 (extreme disease activity). DAS28-hsCRP < 3.2 implied low disease activity and >= 3.2 to <= 5.1 implied moderate disease activity, > 5.1 implied high disease activity. DAS28-hsCRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(hsCRP in mg/L +1) + 0.014* Participant's Global Assessment of Disease Activity + 0.96; ln = natural logarithm, sqrt = square root.
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) at Week 12
time frame: Baseline, Week 12
description: The CDAI was a composite index (without acute-phase reactant) for assessing disease activity. The CDAI was calculated based on following formula: CDAI = 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PhGA where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total CDAI score ranges from 0 to 76, where 0 (none) to 76 (extreme disease activity).
measure: Change From Baseline in Simplified Disease Activity Index (SDAI) at Week 12
time frame: Baseline, Week 12
description: SDAI was numerical sum of 5 outcome parameters: 28 joint count for swelling (SJC28) + 28 joint count for tenderness (TJC28) + GH + PGA + hsCRP where, GH = general health component of the DAS (i.e., Participant's Global Assessment of Disease Activity, assessed using a scale of 0 to 10 centimeter (cm) Visual Analogue Scale (VAS) where 0 = very well and 10 = very poor activity and PhGA = Physician's Global Assessment of Disease Activity assessed using a scale of 0 to 10 cm VAS, where 0 = very well and 10 = very poor activity. The total SDAI score ranges from 0 to 86, where 0 (none) to 86 (extreme disease activity).
measure: Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
time frame: Baseline, Week 12
description: Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
measure: Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
measure: Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
measure: Changes From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
time frame: Baseline, Week 12
description: HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
measure: Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
measure: Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
time frame: Baseline, Week 12
description: hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
measure: Percent Change From Baseline in Tender Joint Count (TJC) and Swollen Joint Count (SJC) at Week 12
time frame: Baseline, Week 12
description: Sixty-eight joints were assessed and classified as tender/not tender and Sixty-six joints were classified as swollen/not swollen by pressure and joint manipulation on physical examination.
measure: Percent Change From Baseline in Participant's Global Assessment of Disease Activity Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The participant's overall assessment of disease activity was recorded using the 100 millimeter (mm) horizontal visual analog scale (VAS). The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity).
measure: Percent Change From Baseline in Participant's Assessment of Pain Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The participants were asked to assess their level of pain by marking a vertical tick on a 100 mm horizontal VAS scale. The scale ranged from 0-100 mm, where 0 indicated no pain and 100 indicated worst possible pain.
measure: Percent Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Total Score at Week 12
time frame: Baseline, Week 12
description: HAQ-DI score was an evaluation of the functional status for a participant. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range: 0-3 where 0 = least difficulty and 3 = extreme difficulty.
measure: Percent Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on Visual Analog Scale (VAS) Score at Week 12
time frame: Baseline, Week 12
description: The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's arthritis disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis).
measure: Percent Change From Baseline in High-Sensitivity C-reactive Protein (hsCRP) at Week 12
time frame: Baseline, Week 12
description: hsCRP was the American College of Rheumatology (ACR) Core Set measure of acute phase reactant. It was measured at the central laboratory to help assess the effect of M2951 on the participant's rheumatoid arthritis.
measure: Change From Baseline in Synovitis Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
time frame: Baseline, Week 12
description: A total of 8 joints in the hand and wrist were evaluated for RAMRIS synovitis. Individual joint scores were assessed on a scale of 0 (no synovitis) to 3 (67 to 100 percent volume enhancement). The final synovitis score was the sum of the individual joint scores. The total score from 8 joints ranges from 0 to 24, with 0 implying normal (no synovitis) and 24 implying 67 to 100 percent volume enhancement.
measure: Change From Baseline in Bone Marrow Edema (Osteitis) Score According to the Outcomes Measures in Rheumatology Clinical Trials Rheumatoid Arthritis Magnetic Resonance Imaging Scoring System (OMERACT RAMRIS) at Week 12
time frame: Baseline, Week 12
description: A total of 25 locations in the hand and wrist were evaluated for RAMRIS bone edema or osteitis. Individual location scores range from 0 (no edema) to 3 (67 to 100 percent involvement of original articular bone) based on the proportion of estimated originally non-eroded bone involved. The final bone edema or osteitis score is the sum of the individual location scores. The total score from the 25 locations ranges from 0 to 75, with 0 implying no bone edema or osteitis and 75 implying 67 to 100 percent involvement of original articular bone.
measure: Change From Baseline in Physical Function Using Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12
time frame: Baseline, Week 12
description: The HAQ-DI questionnaire assessed the participant's self-perception on the degree of difficulty [0 (without any difficulty), 1 (with some difficulty), 2 (with much difficulty), and 3 (unable to do)] when dressing and grooming, arising, eating, walking, hygiene, reaching, gripping, and performing other daily activities. Scores for each functional area were averaged to calculate HAQ-DI scores, which ranged from 0 (no disability) to 3 (worst disability). A decrease in HAQ-DI score indicated an improvement in the participant's condition.
measure: Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score at Week 12
time frame: Baseline, Week 12
description: The 36-Item Short-Form Health Survey (SF-36) was a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) was based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100 = highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100 = highest level of physical functioning).
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Week 12
time frame: Baseline, Week 12
description: The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assess self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.
arm group label: Placebo
arm group type: Placebo Comparator
arm group label: M2951 25 mg QD
arm group type: Experimental
arm group label: M2951 75 mg QD
arm group type: Experimental
arm group label: M2951 50 mg BID
arm group type: Experimental
intervention type: Drug
intervention name: M2591 25 mg QD
description: Participants received 25 milligrams (mg) of M2951 orally once daily (QD) for 12 weeks.
arm group label: M2951 25 mg QD
other name: Evobrutinib
intervention type: Drug
intervention name: M2951 75 mg QD
description: Participants received 75 mg of M2951 orally QD for 12 weeks.
arm group label: M2951 75 mg QD
other name: Evobrutinib
intervention type: Drug
intervention name: M2951 50 mg BID
description: Participants received 50 mg of M2951 orally twice daily (BID) for 12 weeks.
arm group label: M2951 50 mg BID
other name: Evobrutinib
intervention type: Drug
intervention name: Placebo
description: Participants received placebo matched to M2951 orally for 12 weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: EMD Serono Research & Development Institute, Inc.
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country: Argentina
country: Bulgaria
country: Chile
country: Colombia
country: Czechia
country: Mexico
country: Poland
country: Russian Federation
country: Serbia
country: South Africa
country: Ukraine
country: United States
country: Brazil
country: Germany
country: Hungary
country: Romania
country: Slovakia
country: Spain
url: https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200527-0060
description: Trial Awareness and Transparency website
url: https://medical.emdserono.com/en_US/home.html
description: US Medical Information website, Medical Resources
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
sharing ipd: Yes
ipd description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
provided document: 
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