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
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Anti-TNF-alpha; Methotrexate; Placebo; RO7123520
Intervention description: Participants will continue their pre-trial anti-TNF-alpha therapy at a stable dose.; Participants will continue their pre-trial methotrexate therapy at a stable dose.; Participants will receive intravenous infusion of placebo.; Participants will receive intravenous infusion of RO7123520.
Intervention MeSH terms: Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 109.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of adult-onset RA as defined by the ACR 2010 criteria, for at least 6 months
             before screening

          -  Moderately to severely active RA as defined by at least 4/28 tender joints and at
             least 4/28 swollen joints, and a DAS28 greater than or equal to (≥) 3.2

          -  For Part 2 only: Active synovitis and/or osteitis as determined by contrast-enhanced
             magnetic resonance imaging

          -  Participants must be taking stable dose of anti-TNF-alpha therapies

          -  Participants on stable oral glucocorticoids within 6 weeks of planned randomization

          -  Participants taking non-steroidal anti-inflammatory drugs (NSAIDs) intermittently (up
             to 2-3 times weekly) for short-term relief of pain and participants on regular NSAID
             use (on stable dose for ≥ 4 weeks)

        Exclusion Criteria:

          -  Parenteral glucocorticoids administration (intramuscular, IV) of ≥50 mg within 6 weeks
             or less than or equal to (≤) 50 milligrams (mg) within 4 weeks prior to planned
             randomization, or scheduled parenteral administrations during the study

          -  Joint(s) injected with intra-articular glucocorticoids or hyaluronic acid within 6
             weeks prior to planned randomization

          -  Active inflammatory diseases of the joints not related to RA

          -  Systemic autoimmune disease other than RA

          -  Juvenile idiopathic arthritis or juvenile RA and/or RA developed before the age of 16

          -  Active fibromyalgia that makes appropriate assessment of RA disease activity
             challenging in the opinion of the Investigator

          -  RA participants functional status class IV according to the ACR 1991 criteria

          -  Participants with severe chronic or recurrent viral, bacterial, parasitic, or fungal
             infections

          -  History of active hepatitis B virus (HBV), hepatitis C virus (HCV), or human
             immunodeficiency virus (HIV) infection

          -  Any identified confirmed congenital or acquired immunodeficiency

          -  Abnormal laboratory values and liver function test

          -  Myocardial infarction within less than 6 months prior to participation in the study

          -  Severe central or peripheral nervous system diseases