Safety, tolerability, and pharmacokinetics of half-life extended SARS-CoV-2-neutralizing monoclonal antibodies AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults.
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Okada H, Ishikawa K, Itoh Y, Noda Y, Eto T, Pilla Reddy V, Chen CC, Gibbs M, Johnsson E
J Infect Chemother 29 (11) 1061-1067
[2023-11-00; online 2023-07-29]
The aim of this study was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults. In this randomized, double-blind, placebo-controlled, phase 1 study, AZD7442 was administered intramuscularly (300 or 600 mg) or intravenously (300 or 1000 mg) to healthy Japanese adults. Primary endpoints were safety, tolerability, and pharmacokinetics. Anti-drug antibodies and neutralizing antibody activities were secondary endpoints. A total of 40 participants were randomized to receive AZD7442 (n = 30) or placebo (n = 10). Adverse events (AEs) occurred in 12 (40%) and 3 (30%) participants, respectively; there were no deaths, serious AEs, or AEs leading to study withdrawal. Tixagevimab and cilgavimab had mean half-lives of 82.1-95.9 and 77.9-92.0 days, respectively, which were generally similar regardless of administration route. SARS-CoV-2-neutralizing antibody titers were >4-fold higher than baseline levels from Day 8 to Day 211 in participants receiving AZD7442. AZD7442 was well tolerated in healthy Japanese adults, with predictable pharmacokinetics and an extended half-life, consistent with previous studies. gov, NCT04896541.
PubMed 37524201
DOI 10.1016/j.jiac.2023.07.014
Crossref 10.1016/j.jiac.2023.07.014
pii: S1341-321X(23)00181-2
ClinicalTrials.gov: NCT04896541