OX40L Inhibition Suppresses KLH-driven Immune Responses in Healthy Volunteers: A Randomized Controlled Trial Demonstrating Proof-of-Pharmacology for KY1005.
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:
05 2022
05 2022
Historique:
received:
13
10
2021
accepted:
20
01
2022
pubmed:
30
1
2022
medline:
22
4
2022
entrez:
29
1
2022
Statut:
ppublish
Résumé
The safety, tolerability, immunogenicity, and pharmacokinetic (PK) profile of an anti-OX40L monoclonal antibody (KY1005, currently amlitelimab) were evaluated. Pharmacodynamic (PD) effects were explored using keyhole limpet hemocyanin (KLH) and tetanus toxoid (TT) immunizations. Sixty-four healthy male subjects (26.5 ± 6.0 years) were randomized to single doses of 0.006, 0.018, or 0.05 mg/kg, or multiple doses of 0.15, 0.45, 1.35, 4, or 12 mg/kg KY1005, or placebo (6:2). Serum KY1005 concentrations were measured. Antibody responses upon KLH and TT immunizations and skin response upon intradermal KLH administration were performed. PD data were analyzed using repeated measures analysis of covariances (ANCOVAs) and post hoc exposure-response modeling. No serious adverse events occurred and all adverse events were temporary and of mild or moderate severity. A nonlinear increase in mean serum KY1005 concentrations was observed (median time to maximum concentration (T
Identifiants
pubmed: 35092305
doi: 10.1002/cpt.2539
pmc: PMC9314635
doi:
Substances chimiques
Antibodies, Monoclonal
0
OX40 Ligand
0
TNFSF4 protein, human
0
Hemocyanins
9013-72-3
keyhole-limpet hemocyanin
FV4Y0JO2CX
Banques de données
EudraCT
['2016-004839-20']
ClinicalTrials.gov
['NCT03161288']
Types de publication
Journal Article
Randomized Controlled Trial
Langues
eng
Sous-ensembles de citation
IM
Pagination
1121-1132Informations de copyright
© 2022 The Authors. Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.
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