Safety, tolerability, and pharmacokinetics of half-life extended SARS-CoV-2–neutralizing monoclonal antibodies AZD7442 (tixagevimab/cilgavimab) in healthy Japanese adults

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.