Efficacy and Safety of GSK3196165 Versus Placebo and Tofacitinib in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate (contRAst 1)

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 3

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Tofacitinib 5 mg; Drug: Placebo; Biological: GSK3196165 (Otilimab)

Study type: Interventional

Funder types: Industry

Identifiers

NCT03980483

201790

Details and patient eligibility

About

This study [contRAst 1 (201790: NCT03980483)] is a phase 3, randomized, multicenter, double blind study to assess the safety and efficacy of GSK3196165, in combination with methotrexate (MTX), for the treatment of adult participants with moderate to severe active rheumatoid arthritis (RA) who have had an inadequate response to MTX. 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 MTX. 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.

Enrollment: 1,537 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 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 MTX, despite currently taking MTX 15-25 mg/week** oral or injected

  • 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.

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 or Janus kinase (JAK) inhibitors (either experimental or approved)
• Has received prior treatment with a biologic Disease-modifying antirheumatic drug (DMARD) which has been discontinued due to an inadequate response.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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1,537 participants in 6 patient groups, including a placebo group

GSK3196165 90mg + MTX

Experimental group

Description:

Participants received GSK3196165 90 mg subcutaneous (SC) injection once weekly for 52 weeks in combination with methotrexate (MTX).

Treatment:

Biological: GSK3196165 (Otilimab)

GSK3196165 150mg + MTX

Experimental group

Description:

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

Treatment:

Biological: GSK3196165 (Otilimab)

Tofacitinib 5mg + MTX

Active Comparator group

Description:

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

Treatment:

Drug: Tofacitinib 5 mg

Placebo + MTX and GSK3196165 90mg + MTX

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Placebo

Biological: GSK3196165 (Otilimab)

Placebo + MTX and GSK3196165 150mg + MTX

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo

Drug: Placebo

Biological: GSK3196165 (Otilimab)

Placebo + MTX and Tofacitinib 5mg + MTX

Placebo Comparator group

Description:

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

Treatment:

Drug: Tofacitinib 5 mg

Drug: Placebo

Drug: Placebo