Response to Inhibition of Receptor-Interacting Protein Kinase 1 (RIPK1) in Active Plaque Psoriasis: A Randomized Placebo-Controlled Study.
Adult
CD3 Complex
/ metabolism
Canada
Dermis
/ drug effects
Double-Blind Method
Female
Humans
Male
Middle Aged
Oxazepines
/ adverse effects
Protein Kinase Inhibitors
/ adverse effects
Psoriasis
/ diagnosis
Receptor-Interacting Protein Serine-Threonine Kinases
/ antagonists & inhibitors
Remission Induction
Signal Transduction
T-Lymphocytes
/ drug effects
Time Factors
Treatment Outcome
Triazoles
/ adverse effects
Journal
Clinical pharmacology and therapeutics
ISSN: 1532-6535
Titre abrégé: Clin Pharmacol Ther
Pays: United States
ID NLM: 0372741
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
28
10
2019
accepted:
25
03
2020
pubmed:
18
4
2020
medline:
25
5
2021
entrez:
18
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32301501
doi: 10.1002/cpt.1852
pmc: PMC7540322
doi:
Substances chimiques
CD3 Complex
0
GSK2982772
0
Oxazepines
0
Protein Kinase Inhibitors
0
Triazoles
0
RIPK1 protein, human
EC 2.7.11.1
Receptor-Interacting Protein Serine-Threonine Kinases
EC 2.7.11.1
Banques de données
ClinicalTrials.gov
['NCT02776033']
Types de publication
Clinical Trial, Phase II
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
808-816Informations de copyright
© 2020 GlaxoSmithKline. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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