Safety and Pharmacokinetics of Long-Acting Monoclonal Antibodies Tixagevimab and Cilgavimab (AZD7442) in a China Phase 2 Study and Evaluation of Asian Race Effect.

Abstract

Safety, pharmacokinetics, and impact of race of pharmacokinetics on monoclonal antibodies tixagevimab and cilgavimab (AZD7442) were assessed in Chinese adult participants in a Phase 2, randomized, double-blind, placebo-controlled trial. In total, 272 participants were randomized 3:1 to a single intravenous dose of 600 mg AZD7442 or placebo and followed for 451 days. Mean participant age was 34.2 years, 5.9% were aged greater than 60 years, and 69.1% were male. Adverse events (AEs) occurred in 72.8% and 80.0% of participants with AZD7442 and placebo, respectively; most were mild or moderate in severity. Serious AEs were reported in 3.0% and 4.3% of participants with AZD7442 and placebo, respectively. No AEs of special interest, infusion-related reactions, or deaths occurred. Maximum serum concentrations of tixagevimab and cilgavimab were rapidly achieved following infusion, then declined through Day 361. Mean half-lives were 85 days for tixagevimab and 80 days for cilgavimab. AZD7442 recipients exhibited greater than 4-fold neutralizing antibody titer increases versus baseline at Day 8, which then declined through Day 361. Among AZD7442 recipients, 20.8% were treatment-emergent antidrug antibody positive. Asian race had no clinically significant impact on AZD7442 pharmacokinetics. Overall, intravenous 600 mg AZD7442 was well tolerated in Chinese adult participants. AZD7442 pharmacokinetics were similar in Asian and non-Asian participants. ClinicalTrials.gov identifier: NCT05184062.