Last updated: 02/16/2024 10:10:17
Study to evaluate the Efficacy and Safety of GSK3196165 plus Methotrexate in Subjects with Active Moderate-Severe Rheumatoid Arthritis
EudraCT ID
EU CT Number
Not applicable
Trial status
Completed
Completed
Trial overview
Official 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
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Allocation:
Randomized
Primary outcomes:
Proportion of subjects who achieve DAS28(CRP) remission
Timeframe: Week 24
Secondary outcomes:
Change from Baseline in DAS28 (CRP) score
Timeframe: Baseline to Week 62
Disease response rates
Timeframe: Baseline to Week 62
Change from baseline in patient reported outcomes
Timeframe: Baseline to Week 62
Safety and tolerability
Timeframe: Screening to Week 62
Interventions:
Drug: GSK3196165
Drug: MTX
Drug: Folic acid
Drug: Placebo
Enrollment:
222
Observational study model:
Not applicable
Primary completion date:
2017-22-12
Time perspective:
Not applicable
Clinical publications:
C Buckley, J Simon Campos, V Zhdan, K Davy, D Inman, E Fisheleva, A Gupta, M Layton, N Mitchell, J Patel, R Williamson, D Saurigny, P-P Tak, C Hawkes, B Becker. A Phase IIb Dose-Ranging Randomised Study of Efficacy, Patient-Reported Outcomes and Safety of the Anti-Granulocyte Macrophage Colony-Stimulating Factor Antibody Otilimab (GSK3196165) in Patients with Rheumatoid Arthritis. Lancet Rheumatol. 2020;
DOI: 10.1016/S2665-9913(20)30229-0
Medical condition
Arthritis, Rheumatoid
Product
Otilimab
Collaborators
Not applicable
Study date(s)
July 2015 to December 2017
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- Age >=18 years at the time of signing informed consent.
- Meets ACR/EULAR 2010 RA Classification Criteria, with disease duration of >=12 weeks.
- Pregnant or lactating women.
- History of other inflammatory rheumatological or autoimmune disorders, other than Sjögren’s syndrome secondary to RA.
Inclusion and 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.
Trial location(s)
Location
GSK Investigational Site
Koeln, Nordrhein-Westfalen, Germany, 50937
Status
Study Complete
Location
GSK Investigational Site
Panorama / Cape Town, South Africa, 7500
Status
Study Complete
Location
GSK Investigational Site
Uherske Hradiste, Czech Republic, 686 01
Status
Study Complete
Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Completed
Actual primary completion date
2017-22-12
Actual study completion date
2017-29-12
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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