Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis
Condition: Arthritis, Rheumatoid
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: GSK3196165; MTX; Folic acid; Placebo
Intervention description: GSK3196165 is supplied as liquid and will be administered as SC injection.; MTX will be supplied as capsule, tablet or liquid and will be administered orally or as SC injection.; Folic acid will be supplied as capsule, tablet or liquid and will be administered orally.; Placebo is supplied as liquid as sterile 0.9% weight by volume (w/v) sodium chloride solution and will be administered as SC injection
Intervention MeSH terms: Folic Acid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 222.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: DMARD-IR; GSK3196165; Rheumatoid Arthritis

Summary:

      This is a randomised, Phase IIb, dose-adaptive, multicentre, double-blind, parallel group,
      placebo-controlled study with the primary objective to assess the efficacy of GSK3196165, in
      combination with methotrexate (MTX), in subjects with active moderate severe rheumatoid
      arthritis (RA) despite treatment with MTX. Approximately 210 subjects will be randomised into
      the study, following a screening period of up to four weeks. The total treatment period is up
      to 52 weeks, with a 12-week follow-up period after the last dose (Week 50). Subjects will be
      randomised (1:1:1:1:1:1) to placebo or one of five subcutaneous (SC) GSK3196165 doses, in
      combination with MTX (at a weekly dose between 15-25 milligram [mg]), previously received for
      at least 12 weeks, with a stable and tolerated dose and route of administration for >=4
      weeks. Escape therapy is provided at specified timepoints in the protocol for subjects that
      do not achieve adequate disease improvement.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age >=18 years at the time of signing informed consent.

          -  Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks.

          -  Swollen joint count of >=4 (66-joint count) and tender joint count of >=4 (68-joint
             count).

          -  DAS28(CRP) >=3.2.

          -  CRP >=5.0 milligram per litre (mg/L) at screening.

          -  Must have previously received MTX (15-25 mg weekly) 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, e.g. hepatic
             or hematologic toxicity, or per local requirement.

          -  Weight >=45 kilogram (kg).

          -  Male or female subjects are eligible to participate so long as they meet and agree to
             abide by the contraceptive criteria.

          -  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).

        Exclusion Criteria:

          -  Pregnant or lactating women.

          -  History of other inflammatory rheumatological or autoimmune disorders, other than
             Sjögren's syndrome secondary to RA.

          -  History of any respiratory disease which (in the opinion of the investigator) would
             compromise subject safety or the ability of the subject to complete the study (e.g.
             significant interstitial lung disease, such as pulmonary fibrosis, chronic obstructive
             pulmonary disease (COPD), moderate-severe asthma, bronchiectasis, previous pulmonary
             alveolar proteinosis [PAP]).

          -  Clinically-significant or unstable (in the opinion of the investigator) persistent
             cough or dyspnea that is unexplained.

          -  Significant unstable or uncontrolled acute or chronic disease which, in the opinion of
             the investigator, could confound the results of the study or put the subject at undue
             risk.

          -  A history of malignancy.

          -  Hereditary or acquired immunodeficiency disorder, including immunoglobulin deficiency.

          -  Current/previous Hepatitis B virus (HBV), Hepatitis C virus (HCV) or human
             immunodeficiency virus (HIV) 1 or 2 infection.