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

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

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.

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