<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03001219</url>
  </required_header>
  <id_info>
    <org_study_id>BP39261</org_study_id>
    <secondary_id>2016-002126-36</secondary_id>
    <nct_id>NCT03001219</nct_id>
  </id_info>
  <brief_title>A Study of RO7123520 to Evaluate the Safety and Efficacy in Participants With Moderately To Severely Active Rheumatoid Arthritis (RA) Who Are Inadequately Responding to Anti-Tumor Necrosis Factor (TNF)-Alpha Therapy</brief_title>
  <official_title>A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Phase II Study to Evaluate The Safety and Efficacy of RO7123520 as Adjunct Treatment in Patients With Moderately to Severely Active Rheumatoid Arthritis and an Inadequate Response to TNF-alpha Inhibitors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hoffmann-La Roche</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Hoffmann-La Roche</source>
  <brief_summary>
    <textblock>
      This is a Phase IIa/b double-blind, placebo-controlled, randomized, parallel group,&#xD;
      multicenter study to evaluate the safety and efficacy of RO7123520 as adjunctive therapy in&#xD;
      participants with RA who are inadequately responding to standard-of-care (methotrexate and&#xD;
      anti-TNF-alpha therapy). Part 1 of the study will evaluate safety. Part 2 will evaluate&#xD;
      efficacy and safety. Part 3 will evaluate dose-ranging efficacy. Participants will have the&#xD;
      option of continuing to the extension period of the study.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    The trial was prematurely terminated due to a lack of efficacy of the investigational drug.&#xD;
  </why_stopped>
  <start_date type="Actual">December 22, 2016</start_date>
  <completion_date type="Actual">November 6, 2018</completion_date>
  <primary_completion_date type="Actual">November 6, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of Participants With Adverse Events</measure>
    <time_frame>Baseline to last participant last visit (approximately 2 years)</time_frame>
    <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12</measure>
    <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of Participants With Anti-Drug Antibodies</measure>
    <time_frame>Baseline</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans</measure>
    <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12</measure>
    <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12</measure>
    <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving DAS28 Remission at Week 12</measure>
    <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving CDAI Remission at Week 12</measure>
    <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity. CDAI remission is defined as a score of less than or equal to 2.8.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving ACR20 Response at Week 12</measure>
    <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Achieving ACR70 Response at Week 12</measure>
    <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12</measure>
    <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of &lt;3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as &gt;26.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12</measure>
    <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
    <description>The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 &quot;without any difficulty&quot; to 3 &quot;unable to do.&quot; A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum RO7123520 Concentration</measure>
    <time_frame>Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Synovial Fluid RO7123520 Concentration</measure>
    <time_frame>Pre-dose (0 hour) on Days 1, 84</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Actual">109</enrollment>
  <condition>Rheumatoid Arthritis</condition>
  <arm_group>
    <arm_group_label>Part 1: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 1: RO7123520</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: RO7123520</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3: Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.&#xD;
NOTE: Part 3 was not conducted.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 3: RO7123520</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.&#xD;
NOTE: Part 3 was not conducted.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Anti-TNF-alpha</intervention_name>
    <description>Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.</description>
    <arm_group_label>Part 1: Placebo</arm_group_label>
    <arm_group_label>Part 1: RO7123520</arm_group_label>
    <arm_group_label>Part 2: Placebo</arm_group_label>
    <arm_group_label>Part 2: RO7123520</arm_group_label>
    <arm_group_label>Part 3: Placebo</arm_group_label>
    <arm_group_label>Part 3: RO7123520</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Methotrexate</intervention_name>
    <description>Participants will continue their pre-trial methotrexate therapy at a stable dose.</description>
    <arm_group_label>Part 1: Placebo</arm_group_label>
    <arm_group_label>Part 1: RO7123520</arm_group_label>
    <arm_group_label>Part 2: Placebo</arm_group_label>
    <arm_group_label>Part 2: RO7123520</arm_group_label>
    <arm_group_label>Part 3: Placebo</arm_group_label>
    <arm_group_label>Part 3: RO7123520</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive intravenous infusion of placebo.</description>
    <arm_group_label>Part 1: Placebo</arm_group_label>
    <arm_group_label>Part 2: Placebo</arm_group_label>
    <arm_group_label>Part 3: Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>RO7123520</intervention_name>
    <description>Participants will receive intravenous infusion of RO7123520.</description>
    <arm_group_label>Part 1: RO7123520</arm_group_label>
    <arm_group_label>Part 2: RO7123520</arm_group_label>
    <arm_group_label>Part 3: RO7123520</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of adult-onset RA as defined by the ACR 2010 criteria, for at least 6 months&#xD;
             before screening&#xD;
&#xD;
          -  Moderately to severely active RA as defined by at least 4/28 tender joints and at&#xD;
             least 4/28 swollen joints, and a DAS28 greater than or equal to (≥) 3.2&#xD;
&#xD;
          -  For Part 2 only: Active synovitis and/or osteitis as determined by contrast-enhanced&#xD;
             magnetic resonance imaging&#xD;
&#xD;
          -  Participants must be taking stable dose of anti-TNF-alpha therapies&#xD;
&#xD;
          -  Participants on stable oral glucocorticoids within 6 weeks of planned randomization&#xD;
&#xD;
          -  Participants taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (up&#xD;
             to 2-3 times weekly) for short-term relief of pain and participants on regular NSAID&#xD;
             use (on stable dose for ≥ 4 weeks)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Parenteral glucocorticoids administration (intramuscular, IV) of ≥50 mg within 6 weeks&#xD;
             or less than or equal to (≤) 50 milligrams (mg) within 4 weeks prior to planned&#xD;
             randomization, or scheduled parenteral administrations during the study&#xD;
&#xD;
          -  Joint(s) injected with intra-articular glucocorticoids or hyaluronic acid within 6&#xD;
             weeks prior to planned randomization&#xD;
&#xD;
          -  Active inflammatory diseases of the joints not related to RA&#xD;
&#xD;
          -  Systemic autoimmune disease other than RA&#xD;
&#xD;
          -  Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16&#xD;
&#xD;
          -  Active fibromyalgia that makes appropriate assessment of RA disease activity&#xD;
             challenging in the opinion of the Investigator&#xD;
&#xD;
          -  RA participants functional status class IV according to the ACR 1991 criteria&#xD;
&#xD;
          -  Participants with severe chronic or recurrent viral, bacterial, parasitic, or fungal&#xD;
             infections&#xD;
&#xD;
          -  History of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human&#xD;
             immunodeficiency virus (HIV) infection&#xD;
&#xD;
          -  Any identified confirmed congenital or acquired immunodeficiency&#xD;
&#xD;
          -  Abnormal laboratory values and liver function test&#xD;
&#xD;
          -  Myocardial infarction within less than 6 months prior to participation in the study&#xD;
&#xD;
          -  Severe central or peripheral nervous system diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Clinical Trials</last_name>
    <role>Study Director</role>
    <affiliation>Hoffmann-La Roche</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Pinnacle Research Group; Llc, Central</name>
      <address>
        <city>Anniston</city>
        <state>Alabama</state>
        <zip>36207</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis &amp; Rheumatology Associates, P.C.</name>
      <address>
        <city>Glendale</city>
        <state>Arizona</state>
        <zip>85306</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arizona Arthritis and Rheuma</name>
      <address>
        <city>Mesa</city>
        <state>Arizona</state>
        <zip>85202</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>Medvin Clinical Research</name>
      <address>
        <city>Covina</city>
        <state>California</state>
        <zip>91723</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Medical Research, LLC</name>
      <address>
        <city>Lakewood</city>
        <state>California</state>
        <zip>90712</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford hospital &amp; Clinics; Investigational Drug Services</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omega Research Consultants LLC</name>
      <address>
        <city>DeBary</city>
        <state>Florida</state>
        <zip>32713-1817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Marcus Research Clinic, Inc.</name>
      <address>
        <city>Hialeah</city>
        <state>Florida</state>
        <zip>33015-5110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Millenium Research</name>
      <address>
        <city>Ormond Beach</city>
        <state>Florida</state>
        <zip>32174</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinical Pharmacology Study Group</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01610</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shores Rheumatology PC</name>
      <address>
        <city>Saint Clair Shores</city>
        <state>Michigan</state>
        <zip>48080</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Arthritis &amp; Osteoporosis Associates</name>
      <address>
        <city>Freehold</city>
        <state>New Jersey</state>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Atlantic Coast Rheumatology</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08755</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ocean Rheumatology</name>
      <address>
        <city>Toms River</city>
        <state>New Jersey</state>
        <zip>08775</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albuquerque Center For Rheumatology</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albuquerque Clinical Trials</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint Lawrence Health System; Rheumatology</name>
      <address>
        <city>Canton</city>
        <state>New York</state>
        <zip>13617</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Paramount Medical Research</name>
      <address>
        <city>Middleburg Heights</city>
        <state>Ohio</state>
        <zip>44130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Altoona Center For Clinical Research</name>
      <address>
        <city>Duncansville</city>
        <state>Pennsylvania</state>
        <zip>16635</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Advanced Rheumatology &amp; Arthritis Research Center</name>
      <address>
        <city>Wexford</city>
        <state>Pennsylvania</state>
        <zip>15090</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Low Country Rheumatology, PA</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29406</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia Arthritis Center (Partnership Practice)</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>West Tennessee Research Institute</name>
      <address>
        <city>Jackson</city>
        <state>Tennessee</state>
        <zip>38305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Adriana Pop-Moody MD Clinic PA</name>
      <address>
        <city>Corpus Christi</city>
        <state>Texas</state>
        <zip>78404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Metroplex Clinical Research</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75231</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pioneer Research Solutions</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>077099</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77058-3675</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77089</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southwest Rheumatology</name>
      <address>
        <city>Mesquite</city>
        <state>Texas</state>
        <zip>75150</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Accurate Clinical Research, Inc</name>
      <address>
        <city>Stafford</city>
        <state>Texas</state>
        <zip>77477</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Organización medica de Investi</name>
      <address>
        <city>Cap fed</city>
        <zip>1015</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigaciones Reumatologicas y Osteologicas</name>
      <address>
        <city>Ciudad Autonoma de Buenos Aires</city>
        <zip>1111</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cer San Juan</name>
      <address>
        <city>San Juan</city>
        <zip>5400</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Medico Privado de Reumatologia; Reumathology</name>
      <address>
        <city>San Miguel</city>
        <zip>T4000AXL</zip>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Universität Wien, Allgemeines Krankenhaus der Stadt Wien</name>
      <address>
        <city>Wien</city>
        <zip>1090</zip>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral de Reumatologia del Caribe SAS CIRCARIBE SAS</name>
      <address>
        <city>Barranquilla</city>
        <zip>00000</zip>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion en Reumatologia y Especialdades Medicas SAS. CIREEM</name>
      <address>
        <city>Bogota</city>
        <zip>110221</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>Fundación Instituto de Reumatología Fernando Chalem</name>
      <address>
        <city>Bogota</city>
        <zip>111211</zip>
        <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>Healthy Medical Center SAS</name>
      <address>
        <city>Zipaquirá</city>
        <country>Colombia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Research Organisation GmbH</name>
      <address>
        <city>Berlin</city>
        <zip>10117</zip>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Estudio y Tratamiento de Enfermedades Reumaticas</name>
      <address>
        <city>Guatemala</city>
        <country>Guatemala</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Privada de Reumatologia Dr. Henry Briones Alvarado</name>
      <address>
        <city>Guatemala</city>
        <country>Guatemala</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Città della Salute e della Scienza di Torino; Radiology</name>
      <address>
        <city>Torino</city>
        <state>Abruzzo</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero-Universitaria Policlinico S. Orsola Malpighi; U.O. Malattie Infettive</name>
      <address>
        <city>Bologna</city>
        <state>Emilia-Romagna</state>
        <zip>40138</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero - Universitaria Policlinico - Vittorio Emanuele</name>
      <address>
        <city>Catania</city>
        <state>Sicilia</state>
        <zip>95123</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Careggi - SOD Reumatologia</name>
      <address>
        <city>Firenze</city>
        <state>Toscana</state>
        <zip>50134</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion del Noroeste SC</name>
      <address>
        <city>Tijuana</city>
        <state>BAJA California</state>
        <zip>22010</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Investigacion y Biomedicina de Chihuahua, Sociedad Civil</name>
      <address>
        <city>Chichuahua</city>
        <state>Chihuahua</state>
        <zip>31000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Integral en Reumatología S.A. de C.V. (CIRSA)</name>
      <address>
        <city>Guadalajara</city>
        <state>Jalisco</state>
        <zip>44160</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Médico de las Américas</name>
      <address>
        <city>Merida</city>
        <state>Yucatan</state>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Unidad de Atencion Medica e Investigacion en Salud (UNAMIS)</name>
      <address>
        <city>Mérida</city>
        <state>Yucatan</state>
        <zip>97070</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Javier Orozco Private Practice</name>
      <address>
        <city>Guadalajara</city>
        <zip>44650</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigación; Artritis y Osteoporosis S.C.</name>
      <address>
        <city>Mexicali</city>
        <zip>21200</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Angeles Lindavista</name>
      <address>
        <city>Mexico</city>
        <zip>07760</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario &quot;Dr. Jose Eleuterio Gonzalez&quot;</name>
      <address>
        <city>Monterrey</city>
        <zip>64460</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Policlinica Medica de Queretaro S.C.</name>
      <address>
        <city>Queretaro</city>
        <zip>76000</zip>
        <country>Mexico</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hogar Clínica San Juan de Dios</name>
      <address>
        <city>Arequipa</city>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Internacional Sede Lima</name>
      <address>
        <city>LIma</city>
        <zip>Lima 01</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Internacional, Sede San Borja; Unidad de Investigacion de Clínica Internacional</name>
      <address>
        <city>Lima</city>
        <zip>Lima 41</zip>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Instituto de Ginecología y Reproducción</name>
      <address>
        <city>Lima</city>
        <country>Peru</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marques de Valdecilla; Servicio de Reumatologia</name>
      <address>
        <city>Santander</city>
        <state>Cantabria</state>
        <zip>39008</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complexo Hospitalario Universitario A Coruña; Servicio de Reumatología</name>
      <address>
        <city>A Coruña</city>
        <state>LA Coruña</state>
        <zip>15006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Basurto; Servicio de Reumatologia</name>
      <address>
        <city>Bilbao</city>
        <state>Vizcaya</state>
        <zip>48013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario de la Princesa; Servicio de Reumatologia</name>
      <address>
        <city>Madrid</city>
        <zip>28006</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon; Servicio de Reumatología</name>
      <address>
        <city>Madrid</city>
        <zip>28007</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre</name>
      <address>
        <city>Madrid</city>
        <zip>28041</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario Carlos Haya; Servicio de Psiquiatria</name>
      <address>
        <city>Malaga</city>
        <zip>29010</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Reina Sofía; Servicio de Aparato Digestivo</name>
      <address>
        <city>Murcia</city>
        <zip>30003</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Queen Elizabeth Hospital Birmingham</name>
      <address>
        <city>Birmingham</city>
        <zip>B15 2WB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cambridge University Hospitals NHS Foundation Trust</name>
      <address>
        <city>Cambridge</city>
        <zip>CB2 0QQ</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Glasgow Royal Infirmary</name>
      <address>
        <city>Glasgow</city>
        <zip>G4 0SF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Barts Hospital; Department of Rheumatology</name>
      <address>
        <city>London</city>
        <zip>E1 4DG</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Guys and St Thomas NHS Foundation Trust, Guys Hospital</name>
      <address>
        <city>London</city>
        <zip>SE1 9RT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Newcastle U. Medical School; Institute of Cellular Medicine</name>
      <address>
        <city>Newcastle</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Oxford, Botnar Research Centre</name>
      <address>
        <city>Oxford</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Derriford Hospital</name>
      <address>
        <city>Plymouth</city>
        <zip>PL6 8DH</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lister Hospital; Rheumatology Dept</name>
      <address>
        <city>Stevenage</city>
        <zip>SG1 4AB</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Austria</country>
    <country>Colombia</country>
    <country>Germany</country>
    <country>Guatemala</country>
    <country>Italy</country>
    <country>Mexico</country>
    <country>Peru</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <removed_countries>
    <country>Czech Republic</country>
    <country>Czechia</country>
    <country>Poland</country>
  </removed_countries>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>December 20, 2016</study_first_submitted>
  <study_first_submitted_qc>December 20, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 22, 2016</study_first_posted>
  <results_first_submitted>November 4, 2019</results_first_submitted>
  <results_first_submitted_qc>January 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 29, 2020</results_first_posted>
  <last_update_submitted>January 17, 2020</last_update_submitted>
  <last_update_submitted_qc>January 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Methotrexate</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>March 28, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03001219/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Adult men and women with moderate to severe active rheumatoid arthritis (RA) who experience an inadequate response to disease-modifying anti-rheumatic drug (DMARD) therapy with MTX plus anti-TNF-a therapy.</recruitment_details>
      <pre_assignment_details>Arms are not mutually exclusive.&#xD;
Proof of Concept: 109 total participants enrolled.&#xD;
Extension Period Analysis: 106 participants from the previous groups, including placebo, received 360 (n=9) or 810 mg/dose (n=97) of RO7123520.&#xD;
Part 3 was not conducted due to early study termination.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>PoC Placebo to Extension Period Analysis RO7123520</title>
          <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56. Participants from this group that continued to the Extension Period Analysis period were assigned RO7123520 + pre-trial anti-TNF-alpha and MTX at either 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
        <group group_id="P2">
          <title>RO70123520 360 or 810 mg/Dose</title>
          <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56. Participants continuing to the Extension Period Analysis period received 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Proof of Concept</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="72"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="65"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Termination by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Extension Period Analysis</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="97"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="52"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
                <participants group_id="P2" count="45"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Study Termination by Sponsor</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="36"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant Non-Compliance</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Deviation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
                <participants group_id="P2" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>Proof of Concept: A total of 109 participants were enrolled, 37 in the placebo group and 72 in the 810 mg/dose group.&#xD;
Extension Period Analysis: A total of 106 participants from the previous groups received either 360 or 810 mg/dose of RO7123520, with 9 in the 360 mg/dose group and 97 in the 810 mg/dose group.</population>
      <group_list>
        <group group_id="B1">
          <title>PoC Placebo to Extension Period Analysis RO7123520</title>
          <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56. Participants from this group that continued to the Extension Period Analysis period were assigned RO7123520 + pre-trial anti-TNF-alpha and MTX at either 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
        <group group_id="B2">
          <title>RO70123520 360 or 810 mg/Dose</title>
          <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56. Participants continuing to the Extension Period Analysis period received 360 or 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
        <group group_id="B3">
          <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="37"/>
            <count group_id="B2" value="97"/>
            <count group_id="B3" value="134"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <description>Proof of Concept participants</description>
          <population>The proof of concept groups included 37 participants receiving placebo treatment and 72 participants receiving 810 mg/dose of RO7123520.</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="72"/>
                    <count group_id="B3" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54.7" spread="14.1"/>
                    <measurement group_id="B2" value="52.3" spread="12.3"/>
                    <measurement group_id="B3" value="53.1" spread="13.0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <description>Extension Period Analysis participants</description>
          <population>The extension period analysis population contained participants from period 1 of the study. Participants were assigned either 360 (n=9) or 810 (n=97) mg/dose and grouped accordingly.</population>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.6" spread="14.3"/>
                    <measurement group_id="B2" value="53.4" spread="12.8"/>
                    <measurement group_id="B3" value="53.7" spread="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Proof of Concept participants</description>
          <population>The proof of concept groups included 37 participants receiving placebo treatment and 72 participants receiving 810 mg/dose of RO7123520.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="72"/>
                    <count group_id="B3" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="32"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="98"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <description>Extension Period Analysis participants</description>
          <population>The extension period analysis population contained participants from period 1 of the study. Participants were assigned either 360 (n=9) or 810 (n=97) mg/dose and grouped accordingly.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="87"/>
                    <measurement group_id="B3" value="93"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <description>Proof of Concept participants</description>
          <population>The proof of concept groups included 37 participants receiving placebo treatment and 72 participants receiving 810 mg/dose of RO7123520.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="72"/>
                    <count group_id="B3" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="54"/>
                    <measurement group_id="B3" value="81"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="28"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <description>Extension Period Analysis participants</description>
          <population>The extension period analysis population contained participants from period 1 of the study. Participants were assigned either 360 (n=9) or 810 (n=97) mg/dose and grouped accordingly.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="73"/>
                    <measurement group_id="B3" value="74"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="32"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <description>Proof of Concept participants</description>
          <population>The proof of concept groups included 37 participants receiving placebo treatment and 72 participants receiving 810 mg/dose of RO7123520.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="37"/>
                    <count group_id="B2" value="72"/>
                    <count group_id="B3" value="109"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="19"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="52"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <population>The extension period analysis population contained participants from period 1 of the study. Participants were assigned either 360 (n=9) or 810 (n=97) mg/dose and grouped accordingly.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="97"/>
                    <count group_id="B3" value="106"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_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_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="68"/>
                    <measurement group_id="B3" value="75"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Adverse Events</title>
        <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
        <time_frame>Baseline to last participant last visit (approximately 2 years)</time_frame>
        <population>The safety population included all participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adverse Events</title>
          <description>An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.</description>
          <population>The safety population included all participants who received at least one dose of study medication.</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="37"/>
                <count group_id="O2" value="70"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48.6"/>
                    <measurement group_id="O2" value="60.0"/>
                    <measurement group_id="O3" value="66.7"/>
                    <measurement group_id="O4" value="60.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12</title>
        <description>The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
        <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants. Overall study = up to 32 weeks per participant. PoC = Weeks 1-12, Extension Period Analysis = Weeks 1-20 (overall study weeks 13-32)</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12</title>
          <description>The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
          <population>The efficacy population included all randomized participants. Overall study = up to 32 weeks per participant. PoC = Weeks 1-12, Extension Period Analysis = Weeks 1-20 (overall study weeks 13-32)</population>
          <units>Percent</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.2" lower_limit="7.67" upper_limit="29.95"/>
                    <measurement group_id="O2" value="11.1" lower_limit="5.86" upper_limit="19.48"/>
                    <measurement group_id="O3" value="0" lower_limit="0" upper_limit="30.89"/>
                    <measurement group_id="O4" value="1.0" lower_limit="0.07" upper_limit="5.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Percentage of Participants With Anti-Drug Antibodies</title>
        <time_frame>Baseline</time_frame>
        <population>This outcome measure only includes the immunogenicity population, which was the PoC 810 mg dose group. These participants had at least 1 pre-dose ADA assessment.</population>
        <group_list>
          <group group_id="O1">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Anti-Drug Antibodies</title>
          <population>This outcome measure only includes the immunogenicity population, which was the PoC 810 mg dose group. These participants had at least 1 pre-dose ADA assessment.</population>
          <units>Percent</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="69"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans</title>
        <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The safety population included all participants who received at least one dose of study medication.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans</title>
          <population>The safety population included all participants who received at least one dose of study medication.</population>
          <units>g/cm^2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="70"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="67"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="94"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.02" spread="0.21"/>
                    <measurement group_id="O2" value="2.51" spread="12.46"/>
                    <measurement group_id="O3" value="1.17" spread="0.20"/>
                    <measurement group_id="O4" value="2.06" spread="10.53"/>
                  </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="32"/>
                    <count group_id="O2" value="59"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="72"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.06" spread="0.20"/>
                    <measurement group_id="O2" value="0.71" spread="5.50"/>
                    <measurement group_id="O3" value="-0.01" spread="0.04"/>
                    <measurement group_id="O4" value="0.58" spread="4.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12</title>
        <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.</description>
        <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12</title>
          <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.</description>
          <population>The efficacy population included all randomized participants.</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="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="69"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.05" spread="10.99"/>
                    <measurement group_id="O2" value="37.38" spread="13.14"/>
                    <measurement group_id="O3" value="30.89" spread="15.31"/>
                    <measurement group_id="O4" value="32.17" spread="15.91"/>
                  </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="36"/>
                    <count group_id="O2" value="65"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.44" spread="15.11"/>
                    <measurement group_id="O2" value="-14.44" spread="13.96"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12</title>
        <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
        <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12</title>
          <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
          <population>The efficacy population included all randomized participants.</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="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="69"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.29" spread="0.78"/>
                    <measurement group_id="O2" value="6.28" spread="1.03"/>
                    <measurement group_id="O3" value="5.42" spread="1.63"/>
                    <measurement group_id="O4" value="5.82" spread="1.28"/>
                  </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="37"/>
                    <count group_id="O2" value="65"/>
                    <count group_id="O3" value="0"/>
                    <count group_id="O4" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-1.62" spread="1.28"/>
                    <measurement group_id="O2" value="-1.15" spread="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving DAS28 Remission at Week 12</title>
        <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
        <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving DAS28 Remission at Week 12</title>
          <description>The DAS28 is a combined index for measuring disease activity in RA; the &quot;28&quot; refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.</description>
          <population>The efficacy population included all randomized participants.</population>
          <units>Percent</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1.4"/>
                    <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>Percentage of Participants Achieving CDAI Remission at Week 12</title>
        <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity. CDAI remission is defined as a score of less than or equal to 2.8.</description>
        <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving CDAI Remission at Week 12</title>
          <description>The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity. CDAI remission is defined as a score of less than or equal to 2.8.</description>
          <population>The efficacy population included all randomized participants.</population>
          <units>Percent</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="66"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1.4"/>
                    <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>Percentage of Participants Achieving ACR20 Response at Week 12</title>
        <description>The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
        <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving ACR20 Response at Week 12</title>
          <description>The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
          <population>The efficacy population included all randomized participants.</population>
          <units>Percent</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="43.2" lower_limit="29.55" upper_limit="57.94"/>
                    <measurement group_id="O2" value="27.8" lower_limit="19.42" upper_limit="37.88"/>
                    <measurement group_id="O3" value="0" lower_limit="0.00" upper_limit="30.89"/>
                    <measurement group_id="O4" value="11.3" lower_limit="6.66" upper_limit="18.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Achieving ACR70 Response at Week 12</title>
        <description>The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
        <time_frame>Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Achieving ACR70 Response at Week 12</title>
          <description>The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.</description>
          <population>The efficacy population included all randomized participants.</population>
          <units>Percent</units>
          <param>Number</param>
          <dispersion>90% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" lower_limit="0.00" upper_limit="9.15"/>
                    <measurement group_id="O2" value="1.4" lower_limit="0.10" upper_limit="7.04"/>
                    <measurement group_id="O3" value="0" lower_limit="0.00" upper_limit="30.89"/>
                    <measurement group_id="O4" value="0" lower_limit="0.00" upper_limit="3.65"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12</title>
        <description>The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of &lt;3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as &gt;26.</description>
        <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12</title>
          <description>The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of &lt;3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as &gt;26.</description>
          <population>The efficacy population included all randomized participants.</population>
          <units>Scores 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="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="69"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="38.84" spread="10.58"/>
                    <measurement group_id="O2" value="39.02" spread="14.55"/>
                    <measurement group_id="O3" value="31.23" spread="15.25"/>
                    <measurement group_id="O4" value="34.08" spread="16.69"/>
                  </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="34"/>
                    <count group_id="O2" value="65"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="97"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-17.48" spread="14.48"/>
                    <measurement group_id="O2" value="-14.99" spread="15.19"/>
                    <measurement group_id="O3" value="-15.33" spread="18.24"/>
                    <measurement group_id="O4" value="-13.15" spread="14.56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12</title>
        <description>The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 &quot;without any difficulty&quot; to 3 &quot;unable to do.&quot; A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.</description>
        <time_frame>Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)</time_frame>
        <population>The efficacy population included all randomized participants.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12</title>
          <description>The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 &quot;without any difficulty&quot; to 3 &quot;unable to do.&quot; A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.</description>
          <population>The efficacy population included all randomized participants.</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="37"/>
                <count group_id="O2" value="72"/>
                <count group_id="O3" value="9"/>
                <count group_id="O4" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="37"/>
                    <count group_id="O2" value="70"/>
                    <count group_id="O3" value="9"/>
                    <count group_id="O4" value="96"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.63" spread="0.64"/>
                    <measurement group_id="O2" value="1.61" spread="0.76"/>
                    <measurement group_id="O3" value="1.29" spread="0.70"/>
                    <measurement group_id="O4" value="1.59" spread="0.71"/>
                  </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="37"/>
                    <count group_id="O2" value="65"/>
                    <count group_id="O3" value="6"/>
                    <count group_id="O4" value="81"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.15" spread="0.52"/>
                    <measurement group_id="O2" value="-0.24" spread="0.51"/>
                    <measurement group_id="O3" value="-0.21" spread="0.74"/>
                    <measurement group_id="O4" value="-0.21" spread="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Serum RO7123520 Concentration</title>
        <time_frame>Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112</time_frame>
        <population>All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Serum RO7123520 Concentration</title>
          <population>All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Synovial Fluid RO7123520 Concentration</title>
        <time_frame>Pre-dose (0 hour) on Days 1, 84</time_frame>
        <population>All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O2">
            <title>Proof of Concept: RO7123520 810mg/Dose</title>
            <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
          </group>
          <group group_id="O3">
            <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
            <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
          <group group_id="O4">
            <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
            <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
          </group>
        </group_list>
        <measure>
          <title>Synovial Fluid RO7123520 Concentration</title>
          <population>All enrolled participants were included in the PK population. No PK analysis was performed due to an insufficient number of available participant samples for processing.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
                <count group_id="O4" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Baseline to last participant last visit (approximately 2 years)</time_frame>
      <desc>The safety population included participants who received at least one dose of study drug.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>In the Proof of Concept (PoC) period, participants received placebo (IV saline matched to RO7123520) + pre-trial anti-TNF-alpha and methotrexate (MTX), on Days 1, 14, 28, and 56.</description>
        </group>
        <group group_id="E2">
          <title>Proof of Concept: RO7123520 810mg/Dose</title>
          <description>In the PoC period, participants not assigned placebo received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose on Days 1, 14, 28, and 56.</description>
        </group>
        <group group_id="E3">
          <title>Extension Period Analysis: RO7123520 360mg/Dose</title>
          <description>Participants received 360 mg/dose of RO7123520 + pre-trial anti-TNF-alpha and MTX up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
        <group group_id="E4">
          <title>Extension Period Analysis: RO70123520 810mg/Dose</title>
          <description>Participants received RO7123520 + pre-trial anti-TNF-alpha and MTX at 810 mg/dose up to Week 20 of the Extension Period (overall study Week 32).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA v21.1</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="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Arthritis bacterial</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Intervertebral disc protrusion</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Metastatic squamous cell carcinoma</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Tonsil cancer</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA v21.1</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="10" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="17" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphadenopathy</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Flatulence</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="3" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Chronic tonsillitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Folliculitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Laryngitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Upper respiratory tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="2" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="9" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>C-reactive protein increased</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Computerised tomogram abnormal</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypercholesterolaemia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypertriglyceridaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck mass</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Rheumatoid arthritis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="97"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="1" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="37"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="70"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="9"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="97"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.</restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The trial was prematurely terminated due to a lack of efficacy of the investigational drug. There were no serious safety issues or adverse events contributing to the decision to terminate early.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Medical Communications</name_or_title>
      <organization>Hoffmann-La Roche</organization>
      <phone>800-821-8590</phone>
      <email>genentech@druginfo.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/NCT03001219
org study id: BP39261
secondary id: 2016-002126-36
nct id: NCT03001219
lead sponsor: 
This is a Phase IIa/b double-blind, placebo-controlled, randomized, parallel group,
      multicenter study to evaluate the safety and efficacy of RO7123520 as adjunctive therapy in
      participants with RA who are inadequately responding to standard-of-care (methotrexate and
      anti-TNF-alpha therapy). Part 1 of the study will evaluate safety. Part 2 will evaluate
      efficacy and safety. Part 3 will evaluate dose-ranging efficacy. Participants will have the
      option of continuing to the extension period of the study.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percentage of Participants With Adverse Events
time frame: Baseline to last participant last visit (approximately 2 years)
description: An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
measure: Proportion of Participants Achieving an American College of Rheumatology (ACR) 50 Response at Week 12
time frame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The ACR50 is a composite measure defined as both improvement of 50% in the number of tender and number of swollen joints, and a 50% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.
measure: Percentage of Participants With Anti-Drug Antibodies
time frame: Baseline
measure: Change From Baseline in Bone Mineral Density Lumbar Spine L1-L4 as Assessed by Dual Energy X-ray Absorptiometry (DEXA) Scans
time frame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
measure: Change From Baseline in Clinical Disease Activity Index (CDAI) Score at Week 12
time frame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity.
measure: Change From Baseline in Disease Activity Score 28 (DAS28) at Week 12
time frame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The DAS28 is a combined index for measuring disease activity in RA; the "28" refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.
measure: Percentage of Participants Achieving DAS28 Remission at Week 12
time frame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The DAS28 is a combined index for measuring disease activity in RA; the "28" refers to the number of joints included in the assessment. The index includes swollen and tender joint counts, acute phase response, and general arthritis disease activity status. An overall disease activity score of 5.1 or greater implies active disease, less than 3.2 implies low disease activity, and less that 2.6 implies disease remission.
measure: Percentage of Participants Achieving CDAI Remission at Week 12
time frame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The CDAI for Rheumatoid Arthritis (RA) assesses the severity of the disease using clinical data. It consists of the Patient Global disease Activity (PGA) estimate and the Evaluator Global disease Activity (EGA) estimate, each of which represent assessments of disease activity on a scale of 1-10, with 10 being maximum activity. CDAI remission is defined as a score of less than or equal to 2.8.
measure: Percentage of Participants Achieving ACR20 Response at Week 12
time frame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The ACR20 is a composite measure defined as both improvement of 20% in the number of tender and number of swollen joints, and a 20% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.
measure: Percentage of Participants Achieving ACR70 Response at Week 12
time frame: Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The ACR70 is a composite measure defined as both improvement of 70% in the number of tender and number of swollen joints, and a 70% improvement in three of the following five criteria: patient global assessment, physician global assessment, functional ability measure [most often Health Assessment Questionnaire (HAQ)], visual analog pain scale, and erythrocyte sedimentation rate or C-reactive protein (CRP). The ACR is reported as percent improvement at discrete time points.
measure: Change From Baseline in Simple Disease Activity Index (SDAI) Score at Week 12
time frame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The SDAI consists of 5 parameters used to assess RA disease activity: 28-joint count assessments of tenderness and swelling, participant and investigator global assessments, and CRP levels. A composite score is produced, with remission defined as an SDAI of <3.3, low disease activity as ≤11, moderate disease activity as ≤26 and high disease activity as >26.
measure: Change From Baseline in the Stanford Health Assessment Questionnaire Disability Index (HAQ-DI) at Week 12
time frame: Baseline, Week 12 of PoC and Week 12 of Extension Period Analysis (overall study week 24)
description: The HAQ-DI is a 20-item, validated questionnaire used to assess difficulty in performing activities of daily living. The questionnaire assesses eight domains of physical functioning: Dressing and Grooming (2 items), Hygiene (3 items), Arising (2 items), Reach (2 items), Eating (3 items), Grip (3 items), Walking (2 items), Common Daily Activities (3 items). The questions assess usual abilities ranging from 0 "without any difficulty" to 3 "unable to do." A lower HAQ-DI score indicates better quality of life. Subscale scores are combined and the mean value is reported for each arm per timepoint.
measure: Serum RO7123520 Concentration
time frame: Pre-dose (0 hour), 1 hour post infusion (duration of infusion: approximately 1 hour) on Days 1, 14, 28, 56; Pre-dose (0 hour) on Days 84, 112
measure: Synovial Fluid RO7123520 Concentration
time frame: Pre-dose (0 hour) on Days 1, 84
arm group label: Part 1: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
arm group label: Part 1: RO7123520
arm group type: Experimental
description: Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
arm group label: Part 2: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
arm group label: Part 2: RO7123520
arm group type: Experimental
description: Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
arm group label: Part 3: Placebo
arm group type: Placebo Comparator
description: Participants will receive placebo (matched to RO7123520) on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
arm group label: Part 3: RO7123520
arm group type: Experimental
description: Participants will receive RO7123520 on Days 1, 14, 28, and 56 with pre-trial anti-TNF-alpha and methotrexate.
NOTE: Part 3 was not conducted.
intervention type: Drug
intervention name: Anti-TNF-alpha
description: Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.
arm group label: Part 1: Placebo
arm group label: Part 1: RO7123520
arm group label: Part 2: Placebo
arm group label: Part 2: RO7123520
arm group label: Part 3: Placebo
arm group label: Part 3: RO7123520
intervention type: Drug
intervention name: Methotrexate
description: Participants will continue their pre-trial methotrexate therapy at a stable dose.
arm group label: Part 1: Placebo
arm group label: Part 1: RO7123520
arm group label: Part 2: Placebo
arm group label: Part 2: RO7123520
arm group label: Part 3: Placebo
arm group label: Part 3: RO7123520
intervention type: Drug
intervention name: Placebo
description: Participants will receive intravenous infusion of placebo.
arm group label: Part 1: Placebo
arm group label: Part 2: Placebo
arm group label: Part 3: Placebo
intervention type: Drug
intervention name: RO7123520
description: Participants will receive intravenous infusion of RO7123520.
arm group label: Part 1: RO7123520
arm group label: Part 2: RO7123520
arm group label: Part 3: RO7123520
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Clinical Trials
role: Study Director
affiliation: Hoffmann-La Roche
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country: Argentina
country: Austria
country: Colombia
country: Germany
country: Guatemala
country: Italy
country: Mexico
country: Peru
country: Spain
country: United Kingdom
country: United States
country: Czech Republic
country: Czechia
country: Poland
responsible party type: Sponsor
mesh term: Arthritis
mesh term: Arthritis, Rheumatoid
mesh term: Methotrexate
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The trial was prematurely terminated due to a lack of efficacy of the investigational drug. There were no serious safety issues or adverse events contributing to the decision to terminate early.
point of contact: 