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

• Published in: Clinical infectious diseases 2023-04, Vol.76 (7), p.1247-1256
• Main Authors: Levin, Myron J, Ustianowski, Andrew, Thomas, Steven, Templeton, Alison, Yuan, Yuan, Seegobin, Seth, Houlihan, Catherine F, Menendez-Perez, Ibrahim, Pollett, Simon, Arends, Rosalinda H, Beavon, Rohini, Dey, Kanika, Garbes, Pedro, Kelly, Elizabeth J, Koh, Gavin C K W, Ivanov, Stefan, Near, Karen A, Sharbaugh, Audrey, Streicher, Katie, Pangalos, Menelas N, Esser, Mark T
• Format: Article
• Language: English
• Subjects: Adult; COVID-19 - prevention & control; COVID-19 Vaccines; Humans; Major; Post-Exposure Prophylaxis; SARS-CoV-2
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/ciac899

Abstract 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. AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis of coronavirus disease 2019 (COVID-19) did not reduce symptomatic COVID-19 in all participants, but did so in participants who were severe acute respiratory syndrome coronavirus 2 reverse-transcription–polymerase chain reaction–negative/missing at baseline.