Evaluating repeat dosing of GSK2831781 in active ulcerative colitis
Research type
Research Study
Full title
A multicentre randomized, double-blind, placebo-controlled Phase 2 study to evaluate the safety, tolerability, efficacy, dose-response, pharmacokinetics and pharmacodynamics of repeat dosing of an anti-LAG3 cell depleting monoclonal antibody (GSK2831781) in patients with active ulcerative colitis.
IRAS ID
256659
Contact name
Arthur Kaser
Contact email
Sponsor organisation
GlaxoSmithKline Research & Development Limited
Eudract number
2018-003278-28
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Summary of Research
GSK2831781 targets a specific type of cell (Lymphocyte Activation Gene-3 T cell) that is part of the immune system but which if overactive can contribute to inflammation in the body. The particular cells targeted are found in higher numbers in areas of the colon where there is inflammation in patients with ulcerative colitis. These cells may be contributing to the disease, and GSK2831781 is designed to selectively remove them. To date, there has been one study of GSK2831781 in patients with psoriasis. Many of the same types of overactive immune cells found in psoriasis are also found in the colon in ulcerative colitis. In the previous study there was some evidence suggesting that skin inflammation in psoriasis improved.
Approximately 280 participants will take part. Each participant will be in the study for up to 55 weeks.
Participants will be assigned into treatment groups by chance, they will have between a 2 in 3, to a 10 in 11 chance of receiving GSK2831781.GSK2831781 is given by injection, intravenous or subcutaneous.
Study participants will be divided at random into 5 groups. Four groups will take GSK2831781 at different doses. Another group will take placebo. After 10 weeks of treatment, patients whose ulcerative colitis has not improved will receive ‘Open Label Treatment’ and will receive the highest dose of GSK2831781 for another 10 weeks.
Participants will need to visit the clinic up to 17 times over a period of up to 55 weeks and will need to complete all patient questionnaires at visits as well as the short electronic daily symptom diary. Visits to the clinic will vary from 30 minutes up to 6 hours. Following completion of the treatment phase, participants will attend two more visits to the clinic for further blood, stool and urine testing.A pharmaceutical company is funding this research.
Summary of Results
Following initial assessment of data from the planned Interim Analysis 3, in consultation with the DRC, GSK decided to terminate the study, as the efficacy futility criterion was met, and the overall benefit-risk did not support continuation of this study. On review of safety data from this study, GSK considered that the risk-benefit of ongoing participation had become unfavorable such that continued dosing of participants already randomized into the study was not recommended. Investigators were instructed that all participants in this study should discontinue the study drug with immediate effect. The study was terminated early on 14-Jan-2021 and participants were requested to complete early withdrawal and follow-up visits as per protocol, which completed on 17-May-2021.
Due to early termination of the study, the results are primarily focused on the GSK2831781 450 mg IV group and the placebo IV group in the Double-blind Induction Phase.
REC name
East of England - Cambridge Central Research Ethics Committee
REC reference
19/EE/0085
Date of REC Opinion
29 Apr 2019
REC opinion
Favourable Opinion