Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic (cs)/Biologic (b) Disease Modifying Anti-rheumatic Dru

• Status: Active, not recruiting
• Trial end date: 2022-09-22
• Target enrollment: 0
• Participant gender: All

Summary

This study [contRAst 2 (201791: NCT03970837)] is a phase 3, randomized, multicenter, double blind study to assess the safety and efficacy of GSK3196165 in combination with csDMARD(s), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to csDMARD(s) or bDMARD(s). 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 csDMARD(s). 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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: GlaxoSmithKline
• Collaborators: IQVIA; Iqvia Pty Ltd
• Treatments: Antirheumatic Agents; Tofacitinib

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 one or two of the csDMARDs:

• methotrexate (MTX) 15-25 mg/week** oral or injected

• hydroxychloroquine up to 400 mg/day or chloroquine up to 250 mg/day

• sulfasalazine up to 3000 mg/day

• leflunomide up to 20 mg/day***

• bucillamine up to 100 mg/day (or up to 300 mg/day if permitted per local requirement)

• iguratimod up to 50 mg/day

• 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.

• Concomitant use of leflunomide and methotrexate is not allowed, for safety reasons.

Key exclusion criteria

• History of other inflammatory rheumatologic or systemic autoimmune disorder, other than Sjögren's syndrome secondary to RA, that may confound the evaluation of the effect of the study intervention.

• 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).