AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019.

Background: This phase 3 trial assessed AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis against symptomatic coronavirus disease 2019 (COVID-19).
Methods: Adults without prior severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or COVID-19 vaccination were enrolled within 8 days of exposure to a SARS-CoV-2-infected individual and randomized 2:1 to a single 300-mg AZD7442 dose (one 1.5-mL intramuscular injection each of tixagevimab and cilgavimab) or placebo. Primary end points were safety and first post-dose SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR)-positive symptomatic COVID-19 event before day 183.
Results: A total of 1121 participants were randomized and dosed (AZD7442, n = 749; placebo, n = 372). Median (range) follow-up was 49 (5-115) and 48 (20-113) days for AZD7442 and placebo, respectively. Adverse events occurred in 162 of 749 (21.6%) and 111 of 372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23 of 749 (3.1%) and 17 of 372 (4.6%) AZD7442- and placebo-treated participants, respectively (relative risk reduction, 33.3%; 95% confidence interval [CI], -25.9 to 64.7; P = .21). In predefined subgroup analyses of 1073 (96%) participants who were SARS-CoV-2 RT-PCR-negative (n = 974, 87%) or missing an RT-PCR result (n = 99, 9%) at baseline, AZD7442 reduced RT-PCR-positive symptomatic COVID-19 by 73.2% (95% CI, 27.1 to 90.1) vs placebo.
Conclusions: This study did not meet the primary efficacy end point of post-exposure prevention of symptomatic COVID-19. However, analysis of participants who were SARS-CoV-2 RT-PCR-negative or missing an RT-PCR result at baseline support a role for AZD7442 in preventing symptomatic COVID-19. Clinical Trials Registration. NCT04625972.
Competing Interests: Potential conflicts of interest. M. J. L. reports research support from GSK, Johnson & Johnson, Moderna, and Novavax; consultancy for Dynavax, GSK, Merck & Co, Pfizer, and Seqirus; and participation on a data and safety monitoring board (DSMB)/advisory board for GSK. A. U. reports honoraria/speaker fees from Sanofi, Merck, Janssen, GSK, Roche, ViiV, and Gilead; advisory boards for Gilead, Merck, and ViiV/GSK; and participation on a DSMB for COV-Boost study, Flare study, and for Vicore. S. D. P. reports that the USU Infectious Diseases Clinical Research Program (IDCRP), a US Department of Defense institution, and HJF were funded under a cooperative research and development agreement to help conduct the STORM CHASER study, sponsored by AstraZeneca. The HJF, in support of the USU IDCRP, was also funded by the Department of Defense Joint Program Executive Office for Chemical, Biological, Radiological, and Nuclear Defense to augment the conduct of an unrelated phase 3 vaccine trial sponsored by AstraZeneca. Both of these trials were part of the US government COVID-19 response. M. T. E. reports patents planned, issued, or pending by AstraZeneca on AZD7442. P. G. reports consulting fees from Medicago and Takeda Vaccines as senior medical director; a leadership or fiduciary role as a full member of the Academy of Medicine in Rio de Janeiro, Brazil; and stock or stock options in Takeda Pharmaceuticals, AstraZeneca. All authors report medical writing assistance provided by Prime Global. S. T., A. T., Y. Y., S. S., R. H. A., R. B., K. D., P. G., E. J. K., G. C. K. W. K., S. I., K. A. N., A. S., K. S., M. N. P., and M. T. E. are employees of and hold or may hold stock in AstraZeneca. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.
(© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)