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Response to Inhibition of Receptor‐Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo‐Controlled Study
Author(s) -
Weisel Kathleen,
Berger Scott,
Papp Kim,
Maari Catherine,
Krueger James G.,
Scott Nicola,
Tompson Debra,
Wang Susanne,
Simeoni Monica,
Bertin John,
Peter Tak Paul
Publication year - 2020
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt.1852
Subject(s) - placebo , medicine , psoriasis , tolerability , pharmacology , adverse effect , pharmacodynamics , randomized controlled trial , gastroenterology , pharmacokinetics , pathology , immunology , alternative medicine
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.