A 52-week, Phase 3, Multicentre, Randomised, Double Blind, Efficacy and Safety Study Comparing GSK3196165 With Placebo and With Tofacitinib, in Combination With Methotrexate in Participants With Moderately to Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Methotrexate

201790

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.

2019-05-16

2021-09-15

2022-08-16

Completed

Early phase I

1537

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.

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE3'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be randomized to one of six intervention arms in ratio of 6:6:3:1:1:1.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'maskingDescription': 'Double blinded', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 1537, 'type': 'ACTUAL'}}

2024-03-27