Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis

GlaxoSmithKline (GSK)

Status and phase: Completed; Phase 2

Conditions: Arthritis, Rheumatoid

Treatments: Drug: Folic acid; Drug: MTX; Drug: Placebo; Drug: GSK3196165

Study type: Interventional

Funder types: Industry

Identifiers

NCT02504671

2014-003453-34 (EudraCT Number)

201755

Details and patient eligibility

About

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.

Enrollment: 222 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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222 participants in 6 patient groups, including a placebo group

GSK3196165, Dose 1 + MTX and Folic acid

Experimental group

Description:

Subject will receive GSK3196165 Dose 1 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: GSK3196165

Drug: MTX

Drug: Folic acid

GSK3196165, Dose 2 + MTX and folic acid

Experimental group

Description:

Subject will receive GSK3196165 Dose 2 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: GSK3196165

Drug: MTX

Drug: Folic acid

GSK3196165, Dose 3 + MTX and folic acid

Experimental group

Description:

Subject will receive GSK3196165 Dose 3 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: GSK3196165

Drug: MTX

Drug: Folic acid

GSK3196165, Dose 4 + MTX and folic acid

Experimental group

Description:

Subject will receive GSK3196165 Dose 4 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: GSK3196165

Drug: MTX

Drug: Folic acid

GSK3196165, Dose 5 + MTX and folic acid

Experimental group

Description:

Subject will receive GSK3196165 Dose 5 (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: GSK3196165

Drug: MTX

Drug: Folic acid

Placebo + MTX and folic acid

Placebo Comparator group

Description:

Subjects will receive placebo (initially weekly, then every other week) in combination with MTX (at a dose between 15-25 mg/week) and folic acid \>=5 mg/week.

Treatment:

Drug: Placebo

Drug: MTX

Drug: Folic acid