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
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).
Timeline
- Start
- 2019-10-31
- Primary completion
- 2021-09-15
- Completion
- 2022-02-01
Outcome
Missed primary endpoint
paper CONCLUSIONS: Otilimab demonstrated an acceptable safety profile but failed to achieve the primary end point of ACR20 PMID 37696589 ↗
registry analysis (superiority test); GSK3196165 90mg + csDMARD vs Pooled Placebo; p = 0.2868 NCT04134728 ↗
registry analysis (superiority test); GSK3196165 150mg + csDMARD vs Pooled Placebo; p = 0.0596 NCT04134728 ↗
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Otilimab | Monoclonal antibody | 90 mg | Subcutaneous |
| Subject | Otilimab | Monoclonal antibody | 150 mg | Subcutaneous |
| Comparator | Sarilumab | Monoclonal antibody | 200 mg | Subcutaneous |