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

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02504671
• Date of registration: 20/07/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: Study to Evaluate the Efficacy and Safety of GSK3196165 Plus Methotrexate in Subjects With Active Moderate-Severe Rheumatoid Arthritis
• Scientific title: A Phase IIb, Double-Blind, Placebo-Controlled, Dose-Adaptive, Study of the Efficacy and Safety of GSK3196165 in Combination With Methotrexate Therapy, in Subjects With Active Moderate-Severe Rheumatoid Arthritis Despite Treatment With Methotrexate
• Date of first enrolment: July 23, 2015
• Target sample size: 222
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02504671
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
• Phase: Phase 2

Countries of recruitment

Bulgaria, Canada, Czech Republic, Czechia, Estonia, Germany, Hungary, Italy, Mexico, Poland, Russian Federation, South Africa, Spain, Ukraine, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Arthritis, Rheumatoid

Intervention(s)

Drug: Folic acid

Drug: GSK3196165

Drug: MTX

Drug: Placebo

Primary Outcome(s)

Percentage of Participants Who Achieved Disease Activity Score for 28 Different Joints With C-reactive Protein Value (DAS28{CRP}) Remission (DAS28 <2.6) at Week 24 [Time Frame: Week 24]

Secondary Outcome(s)

Change From Baseline in Pain Score at All Assessment Time Points [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and Week 24]

Percentage of Participants With Index-based ACR/EULAR Remission Rates at All Assessment Time Points [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Change From Baseline in CDAI at All Assessment Time Points [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24]

Change From Baseline in DAS28(CRP) at All Assessment Time Points [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24]

Change From Baseline in SDAI at All Assessment Time Points [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24]

Number of Participants With Worst-case Post-Baseline Results for Pulse Oximetry [Time Frame: Up to 62 weeks]

Percentage of Participants With Boolean-based ACR/EULAR Remission Rates at All Assessment Time Points [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue at All Assessment Time Points [Time Frame: Baseline and Weeks 4, 12, 24]

Percentage of Participants in Clinical Disease Activity Index (CDAI) Remission [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at All Assessment Time Points [Time Frame: Baseline and Weeks 1, 2, 4, 6, 8, 12, 16, 20 and 24]

Number of Participants With Serious Infections [Time Frame: Up to 62 weeks]

Percentage of Participants Who Achieved DAS28(CRP) Remission (DAS28 <2.6) at All Time Points [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Number of Participants With Pulmonary Events [Time Frame: Up to 62 weeks]

Time to First DAS28(CRP) Remission [Time Frame: Up to Week 62]

Change From Baseline in Physical and Mental Component Scores (PCS, MCS) and in Domain Scores of Short Form 36 (SF-36) at All Assessment Time Points [Time Frame: Baseline and Weeks 4, 12, 24]

Percentage of Participants Achieving Categorical DAS28(CRP) Response (Moderate/Good [European League Against Rheumatism] EULAR Response) at All Assessment Time Points [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Change From Baseline in Brief Fatigue Inventory (BFI) Question 3 at All Assessment Time Points [Time Frame: Baseline and Weeks 4, 12, 24]

Change From Baseline in DAS28(CRP) at Week 12 [Time Frame: Baseline and Week 12]

Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [Time Frame: Up to 62 weeks]

Number of Participants With Opportunistic Infections [Time Frame: Up to 62 weeks]

Percentage of Participants With American College of Rheumatology's (ACR) 20/50/70 Response Rates at All Assessment Time Points [Time Frame: Weeks 1, 2, 4, 6, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and Week 62 (follow-up)]

Secondary ID(s)

2014-003453-34

201755

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 04/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02504671