Mechanistic Study of GSK3196165 Plus Methotrexate (MTX) in Subjects With Active Rheumatoid Arthritis

Inclusion Criteria

• •Age \>=18 years at the time of signing informed consent.
• •Meets American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) 2010 RA Classification Criteria AND subject not diagnosed before age of 16 years.
• •Functional class I, II or III defined by the 1992 ACR Classification of Functional Status in RA.
• •Active disease as defined by:
• •* Swollen joint count of \>=4 (66-joint count) and tender joint count of \>=4 (68-joint count) at screening and Day 1.
• •AND • Disease activity score for 28 different joints with C-reactive protein (CRP) value (DAS28\[CRP\]) \>=3.2 at screening.
• •AND
• •CRP \>=3.0 milligrams (mg)/liter (L).
• •Signs of inflammation such as synovitis in the MRI scan of the most-affected hand.
• •Must be currently taking MTX (15-25 mg weekly) (oral/injected) for at least 12 weeks before screening, with no change in route of administration, with a stable and tolerated dose for \>=4 weeks prior to Day 1. A stable dose of MTX \>=7.5 mg/week is acceptable, if the MTX dose has been reduced for reasons of documented intolerance to MTX, example (e.g.) hepatic or hematologic toxicity, or per local requirement.
• •Body weight \>=45 kilograms (kg).
• •Male or female subjects are eligible to participate so long as they meet and agree to abide by the contraceptive criteria.
• •Capable of giving signed informed consent as described in protocol which includes compliance with the requirements and restrictions listed in the consent form and in the protocol.
• •Willing to continue or initiate treatment with oral folic acid (at least 5 mg/week) or equivalent and be treated during the entire study (mandatory co-medication for MTX treatment).
• •Diffusing capacity of the lung for carbon monoxide (DLCO) \>=60% predicted; forced expiratory volume in 1 second (FEV1) \>=70% predicted.
• •No evidence of active or latent infection with Mycobacterium tuberculosis (TB).