1. Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study.
- Author
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Weisel K, Berger S, Papp K, Maari C, Krueger JG, Scott N, Tompson D, Wang S, Simeoni M, Bertin J, and Peter Tak P
- Subjects
- Adult, CD3 Complex metabolism, Canada, Dermis enzymology, Dermis immunology, Dermis pathology, Double-Blind Method, Female, Humans, Male, Middle Aged, Oxazepines adverse effects, Protein Kinase Inhibitors adverse effects, Psoriasis diagnosis, Psoriasis enzymology, Psoriasis immunology, Receptor-Interacting Protein Serine-Threonine Kinases metabolism, Remission Induction, Signal Transduction, T-Lymphocytes drug effects, T-Lymphocytes immunology, T-Lymphocytes metabolism, Time Factors, Treatment Outcome, Triazoles adverse effects, Dermis drug effects, Oxazepines therapeutic use, Protein Kinase Inhibitors therapeutic use, Psoriasis drug therapy, Receptor-Interacting Protein Serine-Threonine Kinases antagonists & inhibitors, Triazoles therapeutic use
- Abstract
Receptor-interacting protein kinase 1 (RIPK1), a regulator of inflammation and cell death, is a potential therapeutic target in immune-mediated inflammatory diseases (IMIDs). The objective of this phase IIa multicenter, randomized, double-blind, placebo-controlled study was to evaluate safety, tolerability pharmacokinetics, pharmacodynamics, and preliminary efficacy of GSK2982772, a RIPK1 inhibitor, in plaque-type psoriasis. Psoriasis patients (N = 65) were randomized to 60 mg twice daily (b.i.d.) or three times daily (t.i.d.), or placebo for 84 days. Most adverse events (AEs) were mild with no severe drug-related AEs reported. Plaque Lesion Severity Sum improved with b.i.d. treatment compared with placebo; interpretation of t.i.d. treatment results was complicated by a high placebo response. Reductions in epidermal thickness and infiltration by CD3+ T cells in the epidermis and dermis were observed compared with placebo. Results support the rationale for additional studies on RIPK1 inhibition in IMIDs., (© 2020 GlaxoSmithKline. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)
- Published
- 2020
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