Safety and Efficacy Study of GDC-0853 Compared With Placebo and Adalimumab in Participants With Rheumatoid Arthritis (RA)
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: GDC-0853; Adalimumab; Folic Acid; MTX; Placebo
Intervention description: Participants will receive GDC-0853 at low, mid, or high doses, orally once or twice daily for 12 weeks in Cohort 1 or 2.; Participants will receive adalimumab, subcutaneously Q2W starting on Day 1 for 12 weeks.; Participants will receive stable background therapy of folic acid of at least 5 mg total dose weekly (or equivalent) as per investigator's discretion.; Participants will receive stable background therapy of MTX 15-25 mg/week (oral or parenteral; for participants entering the trial on MTX doses 15 mg/week, doses as low as 7.5 mg/week are allowed only if there is clear documentation in the medical record that higher doses were not tolerated or that the dose of MTX is the highest acceptable dose based on local clinical practice guidelines).; Participants will receive placebo matched to adalimumab, subcutaneously Q2W and/or placebo matched to GDC-0853, orally once or twice daily for 12 weeks in Cohort 1 or 2.
Intervention MeSH terms: Folic Acid; Adalimumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 578.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      This is a multicenter, Phase II, randomized, double-blind, placebo-controlled, active
      comparator (Cohort 1 only), parallel-group, dose-ranging study to evaluate the efficacy and
      safety of GDC-0853 in participants with moderate to severe active RA and an inadequate
      response to previous methotrexate (MTX) therapy (Cohort 1) or MTX and tumor necrosis factor
      (TNF) therapy who may have also had exposure to no more than one non-TNF inhibitor biologic
      (Cohort 2).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Have a diagnosis of adult-onset RA as defined by the 2010 American College of
             Rheumatology/European League Against Rheumatism Classification Criteria for RA

          -  RA disease activity by joint counts and laboratory markers of inflammation: greater
             than or equal to (>=) 6 tender/painful joints on motion (68 joint count) and >= 6
             swollen joints (66 joint count) at both screening and Day 1 (randomization)

          -  For MTX-inadequate response (IR) participants: must have had an inadequate response to
             MTX

          -  For TNF-IR participants: must have had an inadequate response or intolerance to
             previous treatment with at least 1 and no more than 2 biologic TNF-alpha inhibitors
             and may have also been exposed to no more than one biologic non-TNF-alpha inhibitor

          -  High sensitivity C-reactive protein of >= 0.400 milligrams per deciliter (mg/dL) for
             Cohort 1 and >= 0.650 mg/dL for Cohort 2 at screening

        Exclusion Criteria:

          -  History of or current inflammatory joint disease other than RA or other systemic
             autoimmune disorder

          -  For MTX-IR participants: History of treatment with any TNF inhibitor, including
             biosimilar equivalents and history of treatment with biologic non-TNF-alpha inhibitor
             for RA

          -  For all participants: Previous treatment with cell-depleting therapy including B
             cell-depleting therapy (e.g., anti-cluster of differentiation 20-directed therapy such
             as rituximab), tofacitinib, or other Janus kinase inhibitor(s), or alkylating agents

          -  Current treatment with medications that are well known to prolong the QT interval at
             doses that have a clinically meaningful effect on QT

          -  History of non-gallstone-related pancreatitis or chronic pancreatitis

          -  Evidence of serious uncontrolled concomitant cardiac, neurologic, pulmonary, renal,
             hepatic, endocrine, metabolic, or gastrointestinal disease

          -  Evidence of chronic and/or active hepatitis B or C

          -  Women who are pregnant, nursing (breast feeding), or intending to become pregnant
             during the study or within 60 days after completion of the study