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)

Conditions

• Arthritis, Rheumatoid

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• GSK3196165 (Otilimab) — BIOLOGICAL
  GSK3196165 solution in vial/pre-filled syringe (PFS) was administered SC.
• Tofacitinib — DRUG
  Tofacitinib capsule (over encapsulated 5mg tablet) was administered orally.
• Placebo — DRUG
  Placebo matching GSK3196165 and Tofacitinib was administered.

Study Details

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.

Key Dates

Start date

Jun 5, 2019

Status verified

Nov 2023

Primary completion

Oct 29, 2021

Completion

Jan 18, 2023

Study Design

Enrollment

1,764 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: GSK3196165 90mg + csDMARD (Global Cohort)
  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).
• Experimental: GSK3196165 150mg + csDMARD (Global Cohort)
  Participants in Global Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
• Active Comparator: Tofacitinib 5mg + csDMARD (Global Cohort)
  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.
• Placebo Comparator: Placebo + csDMARD and GSK3196165 90mg + csDMARD (Global Cohort)
  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.
• Placebo Comparator: Placebo +csDMARD and GSK3196165 150mg +csDMARD (Global Cohort)
  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.
• Placebo Comparator: Placebo +csDMARD and Tofacitinib 5mg +csDMARD (Global Cohort)
  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.
• Experimental: GSK3196165 90mg + csDMARD (Asia Cohort)
  Participants in Asia Cohort received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
• Experimental: GSK3196165 150mg + csDMARD (Asia Cohort)
  Participants in Asia Cohort received GSK3196165 150 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with csDMARD.
• Active Comparator: Tofacitinib 5mg + csDMARD (Asia Cohort)
  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.
• Placebo Comparator: Placebo + csDMARD and GSK3196165 90mg + csDMARD (Asia Cohort)
  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.
• Placebo Comparator: Placebo + csDMARD and GSK3196165 150mg + csDMARD (Asia Cohort)
  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.
• Placebo Comparator: Placebo + csDMARD and Tofacitinib 5mg + csDMARD (Asia Cohort)
  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.

Primary Outcome Measure

Percentage (%) of Participants With 20% Improvement in American College of Rheumatology Criteria (ACR20) at Week 12 Superiority Comparison With Placebo (Global Cohort) [ Time Frame: Week 12 ]

Locations (64)

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