Efficacy and Safety of GSK3196165 (Otilimab) Versus Placebo and Sarilumab in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Biological Disease-modifying Antirheumatic Drug (DMARDs) and/or Janus Kinase (JAK) Inhibitors
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: GSK3196165 (Otilimab); Sarilumab; Placebo to GSK3196165/ Sarilumab; csDMARDs
Intervention description: GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Sarilumab solution in PFS to be administered SC.; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/PFS to be administered SC.; Stable dose of csDMARD(s) as SoC.
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized to one of six intervention arms in ratio of 6:6:6:1:1:1
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking description: Double blinded
Enrollment: 550.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: bDMARD; GSK3196165; Rheumatoid Arthritis; Sarilumab; Otilimab

Summary:

      This study (contRAst 3 [202018: NCT04134728]) is a Phase 3, randomized, multicenter,
      double-blind study to assess the safety and efficacy of GSK3196165 in combination with
      conventional (cs) DMARD[s]) or the treatment of adult participants with moderate to severe
      active rheumatoid arthritis (RA) who have had an inadequate response to biologic (b)
      DMARD[s]) and/or JAK inhibitors. The study will consist of a screening phase of up to 6 weeks
      followed by 24 week treatment phase in which participants will be randomized in ratio of
      6:6:6:1:1:1 to GSK3196165 150 milligrams (mg) subcutaneously (SC) weekly,GSK3196165 90 mg SC
      weekly, sarilumab 200 mg SC every other week or placebo (three arms) respectively, all in
      combination with background csDMARD(s). At Week 12, participants in the three placebo arms
      will switch from placebo to active intervention (either GSK3196165 150 mg SC weekly,
      GSK3196165 90 mg SC weekly, or sarilumab 200 mg SC every other week). Participants who, in
      investigator's judgement will benefit from extended treatment with GSK3196165, may be
      included in the long-term extension study (contRAst X [209564: NCT04333147]). Any participant
      who does not transition into study 209564 will undergo a safety follow-up visit at Week 34
      (corresponding to 12 weeks after the last potential dose of sarilumab, at Week 22).
    

Eligibility criteria:

        Key inclusion criteria:

          -  >=18 years of age

          -  Has had RA for >=6 months and was not diagnosed before 16 years of age

          -  Has active disease, as defined by having both:*

               -  >=6/68 tender/painful joints (tender joint count [TJC]), and

               -  >=6/66 swollen joints (swollen joint count [SJC])

          -  Has had an inadequate response despite currently taking at least one and at the most
             two concomitant csDMARDs for at least 12 weeks, from the following:

               -  Methotrexate (MTX)

               -  Hydroxychloroquine or chloroquine

               -  Sulfasalazine

               -  Leflunomide

               -  Bucillamine

               -  Iguratimod

               -  Tacrolimus

          -  Has had inadequate response to at least one bDMARD at an approved dose and/or at least
             one JAK inhibitors at an approved dose. In both cases this may be with or without
             combination with a csDMARD.

               -  If surgical treatment of a joint has been performed, that joint cannot be counted
                  in the TJC or SJC.

        Key exclusion criteria:

          -  Has had any active and/or recurrent infections (excluding recurrent fungal infections
             of the nail bed) or has required management of acute or chronic infections.

          -  Has received prior treatment with an antagonist of GM-CSF or its receptor.

          -  Has known infection with human immunodeficiency virus (HIV) or current acute or
             chronic hepatitis B and/or hepatitis C.