Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: GSK3196165 (Otilimab); Tofacitinib 5 mg; Placebo; Placebo
Intervention description: GSK3196165 solution in vial/pre-filled syringe (PFS) to be administered SC.; Tofacitinib cap (over encapsulated 5mg tablet) to be administered orally.; Placebo sterile 0.9 percentage (%) weight by volume (w/v) sodium chloride solution in vial/pre-filled syringe (PFS) to be administered SC.; Placebo cap (containing lactose) to be administered orally.
Intervention MeSH terms: Tofacitinib
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 6:6:3:1:1:1.
Masking: Double (Participant, Investigator)
Masking description: Double blinded
Enrollment: 1537.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Rheumatoid arthritis; GSK3196165; Otilimab; Tofacitinib; Methotrexate; Placebo

Summary:

      This study [contRAst 1 (201790: NCT03980483)] is a phase 3, randomized, multicenter, double
      blind study to assess the safety and efficacy of GSK3196165, in combination with methotrexate
      (MTX), for the treatment of adult participants with moderate to severe active rheumatoid
      arthritis (RA) who have had an inadequate response to MTX. The study will consist of a
      screening phase of up to 6 weeks followed by a 52-week treatment phase in which participants
      will be randomized in a ratio of 6:6:3:1:1:1 to receive GSK3196165 150 milligrams (mg)
      subcutaneous (SC) weekly, GSK3196165 90 mg SC weekly, tofacitinib capsules (cap) 5 mg twice a
      day or placebo (three arms, each placebo arm will have 12 weeks placebo followed by 40 weeks
      active treatment) respectively, all in combination with MTX. 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)]. For those
      participants who do not continue into the long term-extension study, there will be an 8 week
      safety follow-up visit following the treatment phase.
    

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 joint count (TJC), and

               -  >=6/66 swollen joint count (SJC)

          -  Has at least 1 bone erosion present on hand/wrist or foot radiographs

          -  Has had an inadequate response to MTX, despite currently taking MTX 15-25 mg/week**
             oral or injected

               -  If surgical treatment of a joint has been performed, that joint cannot be counted
                  in the TJC or SJC.

                    -  A lower dose of 7.5 mg/week is acceptable if reduced for reasons of
                       intolerance to MTX or per local requirement.

        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 or Janus
             kinase (JAK) inhibitors (either experimental or approved)

          -  Has received prior treatment with a biologic Disease-modifying antirheumatic drug
             (DMARD) which has been discontinued due to an inadequate response.