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J Infect Dis
. 2023 Jan 23;jiad014.
doi: 10.1093/infdis/jiad014. Online ahead of print.
Safety, Tolerability and Pharmacokinetics of Half-Life Extended SARS-CoV-2 Neutralizing Monoclonal Antibodies AZD7442 (Tixagevimab/Cilgavimab) in Healthy Adults
Pablo Forte-Soto 1 , Muna Albayaty 1 2 , Dennis Brooks 3 , Rosalinda H Arends 4 , John Tillinghast 5 , Anastasia A Aksyuk 6 , Jerome Bouquet 7 , Cecil Chen 7 , Asfiha Gebre 4 , Robert J Kubiak 4 , Venkatesh Pilla Reddy 8 , Seth Seegobin 9 , Katie Streicher 6 , Alison Templeton 9 , Mark T Esser 10
Affiliations
- PMID: 36683419
- DOI: 10.1093/infdis/jiad014
Abstract
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).
Keywords: COVID-19; SARS-CoV-2; monoclonal antibody; pharmacokinetics; phase 1; safety; tolerability.