Safety, Tolerability and Pharmacokinetics of Half-Life Extended Severe Acute Respiratory Syndrome Coronavirus 2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab-Cilgavimab) in Healthy Adults.

Background AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)−specific neutralizing monoclonal antibodies (tixagevimab and cilgavimab). Methods This phase 1, first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study evaluated AZD7442 administered intramuscularly (300 mg) or intravenously (300, 1000, or 3000 mg) in healthy adults (aged 18–55 years). The primary end point was safety and tolerability. Secondary end points included pharmacokinetics and antidrug antibodies. Results Between 18 August and 16 October 2020, a total of 60 participants were enrolled; 50 received AZD7442, and 10 received placebo. Adverse events (all of mild or moderate intensity) occurred in 26 participants (52.0%) in the AZD7442 groups and 8 (80.0%) in the placebo group. No infusion or injection site or hypersensitivity reactions occurred. Tixagevimab and cilgavimab had mean half-lives of approximately 90 days (range, 87.0–95.3 days for tixagevimab and 79.8–-91.1 days for cilgavimab) and similar pharmacokinetic profiles over the 361-day study period. SARS-CoV-2–specific neutralizing antibody titers provided by AZD7442 were maintained above those in plasma from convalescent patients with coronavirus disease 2019 (COVID-19). Conclusions AZD7442 was well tolerated in healthy adults, showing a favorable safety profile across all doses. Depending on the SARS-CoV-2 variant, pharmacokinetic analyses suggest the AZD7442 could offer protection for ≥6 months against symptomatic COVID-19 after a single 300-mg intramuscular administration. Clinical trials registration NCT04507256. [ABSTRACT FROM AUTHOR]