Safety, Tolerability, and Pharmacokinetics of the Long-Acting SARS-CoV-2-Neutralizing Monoclonal Antibody Combination AZD7442 (Tixagevimab/Cilgavimab) in Healthy Chinese Adults.

AZD7442, a combination of extended half-life monoclonal antibodies tixagevimab and cilgavimab, was shown to neutralize previously circulating SARS-CoV-2 variants. This study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of AZD7442 in healthy Chinese adults. In this randomized, placebo-controlled, Phase 1 study, AZD7442 was administered intramuscularly or intravenously (300 or 600 mg). End points included safety, tolerability, pharmacokinetics, antidrug antibodies, and SARS-CoV-2-neutralizing antibody titers. Sixty participants were randomized and dosed (AZD7442, n = 49; placebo, n = 11). Adverse events occurred in 45 (91.8%) and 9 (81.8%) participants, serious adverse events occurred in 2 (4.1%) and 0 (0%) participants in AZD7442 and placebo groups, respectively, and there were no deaths. Tixagevimab and cilgavimab had mean half-lives of 82.4-88.1 (range across dosing groups) and 79.0-83.7 days, respectively. In participants who received AZD7442, 3 (6.1%) were treatment-emergent antidrug antibody positive. SARS-CoV-2-neutralizing antibody titers were more than 4-fold higher than baseline levels by Day 8, then decreased through Day 361 following AZD7442 administration. AZD7442 was well tolerated in healthy Chinese adults, demonstrating predictable pharmacokinetics and an extended half-life consistent with previous studies.