Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study.

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.