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 (contRAst 3)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Arthritis, Rheumatoid

Treatments: Biological: GSK3196165 (Otilimab); Drug: csDMARDs; Biological: Sarilumab; Drug: Placebo to GSK3196165/ Sarilumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT04134728

202018

Details and patient eligibility

About

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).

Enrollment: 550 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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 joints (tender joint count [TJC]), and
  • >=6/66 swollen joints (swollen joint count [SJC])

• Has had an inadequate response despite currently taking at least one and at the most two concomitant csDMARDs for at least 12 weeks, from the following:

  • Methotrexate (MTX)
  • Hydroxychloroquine or chloroquine
  • Sulfasalazine
  • Leflunomide
  • Bucillamine
  • Iguratimod
  • Tacrolimus

• Has had inadequate response to at least one bDMARD at an approved dose and/or at least one JAK inhibitors at an approved dose. In both cases this may be with or without combination with a csDMARD.

  • If surgical treatment of a joint has been performed, that joint cannot be counted in the TJC or SJC.

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.
• Has known infection with human immunodeficiency virus (HIV) or current acute or chronic hepatitis B and/or hepatitis C.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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550 participants in 6 patient groups, including a placebo group

GSK3196165 90 mg

Experimental group

Description:

Entire treatment period (24 Weeks): GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as standard of care (SoC).

Treatment:

Biological: GSK3196165 (Otilimab)

Drug: csDMARDs

GSK3196165 150 mg

Experimental group

Description:

Entire treatment period (24 Weeks): GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Treatment:

Biological: GSK3196165 (Otilimab)

Drug: csDMARDs

Sarilumab 200 mg

Active Comparator group

Description:

Entire treatment period (24 Weeks): Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.

Treatment:

Biological: Sarilumab

Drug: csDMARDs

Drug: Placebo to GSK3196165/ Sarilumab

Placebo sequence 1

Placebo Comparator group

Description:

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 90 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Treatment:

Biological: GSK3196165 (Otilimab)

Drug: csDMARDs

Drug: Placebo to GSK3196165/ Sarilumab

Placebo sequence 2

Placebo Comparator group

Description:

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: GSK3196165 150 mg SC injection once weekly. Participants will also receive a stable dose of csDMARD(s) as SoC.

Treatment:

Biological: GSK3196165 (Otilimab)

Drug: csDMARDs

Drug: Placebo to GSK3196165/ Sarilumab

Placebo sequence 3

Placebo Comparator group

Description:

From Week 0-11: Placebo SC injection once weekly. From Week 12 onwards: Sarilumab 200 mg SC injection every other week + placebo SC injection in the intervening weeks. Participants will also receive a stable dose of csDMARD(s) as SoC.

Treatment:

Biological: Sarilumab

Drug: csDMARDs

Drug: Placebo to GSK3196165/ Sarilumab