In The Journal of infectious diseases ; h5-index 82.0
BACKGROUND : AZD7442 is a combination of extended half-life, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific neutralizing monoclonal antibodies (tixagevimab/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, 3000 mg) in healthy adults (aged 18-55 years). The primary endpoint was safety and tolerability. Secondary endpoints included pharmacokinetics and anti-drug antibodies.
RESULTS : Between August 18-October 16, 2020, 60 participants enrolled; 50 received AZD7442 and 10 received placebo. Adverse events (all of mild/moderate intensity) occurred in 26 (52.0%) and 8 (80.0%) participants (AZD7442 and placebo groups, respectively). 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 [tixagevimab], 79.8--91.1 [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 coronavirus disease-19 (COVID-19) patients.
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 AZD7442 could offer protection for at least 6 months against symptomatic COVID-19 following a single 300 mg intramuscular administration.
CLINICAL TRIALS REGISTRATION : NCT04507256 (https://clinicaltrials.gov/ct2/show/NCT04507256).
Forte-Soto Pablo, Albayaty Muna, Brooks Dennis, Arends Rosalinda H, Tillinghast John, Aksyuk Anastasia A, Bouquet Jerome, Chen Cecil, Gebre Asfiha, Kubiak Robert J, Pilla Reddy Venkatesh, Seegobin Seth, Streicher Katie, Templeton Alison, Esser Mark T
COVID-19, SARS-CoV-2, monoclonal antibody, pharmacokinetics, phase 1, safety, tolerability