Journal article
A randomized, placebo-controlled experimental medicine study of RIPK1 inhibitor GSK2982772 in patients with moderate to severe rheumatoid arthritis
- Abstract:
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Background Receptor-interacting protein kinase 1 (RIPK1) is a key mediator of inflammation through cell death and proinflammatory cytokine production. This multicenter, randomized, double-blind (sponsor-unblinded), placebo-controlled, experimental medicine study evaluated the safety, pharmacokinetics (PK), and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in moderate to severe rheumatoid arthritis (RA).
Methods Patients with moderate to severe RA who had received ≥12 weeks’ stable-dose conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy were randomized (2:1) to GSK2982772 60 mg or placebo orally 2 or 3 times daily for 84 days. Safety, PK, disease activity, joint damage, and pharmacodynamic (PD) biomarkers were assessed at days 43 and 85.
Results A total of 52 patients were randomized (placebo, 18; GSK2982772, 34). Adverse events (AEs) were reported in 13 (72%) in patients in the placebo group (n = 3 b.i.d; n = 10 t.i.d.) and 20 (61%) in the GSK2982772 group (n = 3 b.i.d; n = 17 t.i.d.). All treatment-related AEs were mild/moderate, except one severe case of alopecia areata at day 49 and retinal vein thrombosis at day 66 (which led to withdrawal from the study) in patients receiving GSK2982772 t.i.d. Disease Activity Score in 28 Joints–C-reactive protein (DAS28-CRP) scores, ACR20/50/70 response, and rates of low disease activity and remission were similar between placebo and GSK2982772 arms.
Conclusions These results suggest that inhibition of RIPK1 activity at the GSK2982772 exposure levels evaluated do not translate into meaningful clinical improvement of RA.
Trial registration ClinicalTrials.gov Identifier: NCT02858492. Registered 8 August 2016.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Publisher copy:
- 10.1186/s13075-021-02468-0
Authors
- Publisher:
- BioMed Central
- Journal:
- Arthritis Research & Therapy More from this journal
- Volume:
- 23
- Issue:
- 1
- Article number:
- 85
- Publication date:
- 2021-03-16
- Acceptance date:
- 2021-02-26
- DOI:
- EISSN:
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1478-6362
- Language:
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English
- Keywords:
- Pubs id:
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1168923
- Local pid:
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pubs:1168923
- Deposit date:
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2021-03-22
Terms of use
- Copyright holder:
- Weisel et al.
- Copyright date:
- 2021
- Rights statement:
- © The Authors 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.
- Licence:
- CC Attribution (CC BY)
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