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 Drugs (DMARDs)
(contRAst 2 Trial)

Recruiting in Palo Alto (17 mi)

+252 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Waitlist Available

Sponsor: GlaxoSmithKline

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Research Team

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Eligibility Criteria

Inclusion Criteria

You have a minimum age of 18 years.

Key inclusion criteria

You have a swollen joint count of at least 6/66.

See 7 more

Treatment Details

Interventions

csDMARDs (Drug)
GSK3196165 (Otilimab) (Monoclonal Antibodies)
Placebo to GSK3196165 (Otilimab) (Drug)
Placebo to Tofacitinib (Drug)
Tofacitinib (Janus Kinase (JAK) Inhibitor)

Participant Groups

12Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: GSK3196165 90mg + csDMARD (Global Cohort)Experimental Treatment1 Intervention

Participants in Global Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARD).

Group II: GSK3196165 90mg + csDMARD (Asia Cohort)Experimental Treatment1 Intervention

Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Group III: GSK3196165 150mg + csDMARD (Global Cohort)Experimental Treatment1 Intervention

Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Group IV: GSK3196165 150mg + csDMARD (Asia Cohort)Experimental Treatment1 Intervention

Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.

Group V: Tofacitinib 5mg + csDMARD (Asia Cohort)Active Control1 Intervention

Participants in Asia Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks.

Group VI: Tofacitinib 5mg + csDMARD (Global Cohort)Active Control1 Intervention

Participants in Global Cohort received Tofacitinib 5mg capsule, orally, twice daily (BID) in combination with csDMARD plus placebo injection weekly to maintain the blind for 52 weeks.

Group VII: Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)Placebo Group2 Interventions

Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks.

Group VIII: Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)Placebo Group2 Interventions

Participants in Asia Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks.

Group IX: Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)Placebo Group2 Interventions

Participants in Asia Cohort received Placebo capsule BID in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind for 52 weeks.

Group X: Placebo + csDMARD and GSK3196165 90mg + csDMARD (Global Cohort)Placebo Group2 Interventions

Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 90 mg, SC injection, once weekly in combination with csDMARD until 52 weeks.

Group XI: Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)Placebo Group2 Interventions

Participants in Global Cohort received Placebo weekly SC injection in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo to GSK3196165 150 mg, SC injection, once weekly in combination with csDMARD until 52 weeks.

Group XII: Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)Placebo Group2 Interventions

Participants in Global Cohort received Placebo capsule BID in combination with csDMARD for 12 weeks. At week 12, participants were switched from placebo capsule to Tofacitinib 5mg, capsule, orally, BID in combination with csDMARD plus placebo injection to maintain the blind for 52 weeks.