tetano
Editor, Senior Moderator
Clin Infect Dis
. 2022 Nov 22;ciac899.
doi: 10.1093/cid/ciac899. Online ahead of print.
AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19
Myron J Levin[SUP] 1 [/SUP], Andrew Ustianowski[SUP] 2 [/SUP], Steven Thomas[SUP] 3 [/SUP], Alison Templeton[SUP] 4 [/SUP], Yuan Yuan[SUP] 3 [/SUP], Seth Seegobin[SUP] 4 [/SUP], Catherine F Houlihan[SUP] 5 6 [/SUP], Ibrahim Menendez-Perez[SUP] 7 [/SUP], Simon Pollett[SUP] 8 9 [/SUP], Rosalinda H Arends[SUP] 10 [/SUP], Rohini Beavon[SUP] 11 [/SUP], Kanika Dey[SUP] 12 [/SUP], Pedro Garbes[SUP] 12 [/SUP], Elizabeth J Kelly[SUP] 13 [/SUP], Gavin C K W Koh[SUP] 11 [/SUP], Stefan Ivanov[SUP] 14 [/SUP], Karen A Near[SUP] 12 [/SUP], Audrey Sharbaugh[SUP] 15 [/SUP], Katie Streicher[SUP] 13 [/SUP], Menelas N Pangalos[SUP] 16 [/SUP], Mark T Esser[SUP] 17 [/SUP]
Affiliations
Abstract
Background: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19).
Methods: Adults without prior 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 consecutively) or placebo. Primary endpoints 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: 1121 participants were randomized and dosed (mean age 46 years; 49% females; 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 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (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) versus placebo.
Conclusions: This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined 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.
Keywords: AZD7442; COVID-19; SARS-CoV-2; monoclonal antibodies; post-exposure prophylaxis.
. 2022 Nov 22;ciac899.
doi: 10.1093/cid/ciac899. Online ahead of print.
AZD7442 (Tixagevimab/Cilgavimab) for Post-exposure Prophylaxis of Symptomatic COVID-19
Myron J Levin[SUP] 1 [/SUP], Andrew Ustianowski[SUP] 2 [/SUP], Steven Thomas[SUP] 3 [/SUP], Alison Templeton[SUP] 4 [/SUP], Yuan Yuan[SUP] 3 [/SUP], Seth Seegobin[SUP] 4 [/SUP], Catherine F Houlihan[SUP] 5 6 [/SUP], Ibrahim Menendez-Perez[SUP] 7 [/SUP], Simon Pollett[SUP] 8 9 [/SUP], Rosalinda H Arends[SUP] 10 [/SUP], Rohini Beavon[SUP] 11 [/SUP], Kanika Dey[SUP] 12 [/SUP], Pedro Garbes[SUP] 12 [/SUP], Elizabeth J Kelly[SUP] 13 [/SUP], Gavin C K W Koh[SUP] 11 [/SUP], Stefan Ivanov[SUP] 14 [/SUP], Karen A Near[SUP] 12 [/SUP], Audrey Sharbaugh[SUP] 15 [/SUP], Katie Streicher[SUP] 13 [/SUP], Menelas N Pangalos[SUP] 16 [/SUP], Mark T Esser[SUP] 17 [/SUP]
Affiliations
- PMID: 36411267
- DOI: 10.1093/cid/ciac899
Abstract
Background: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 (COVID-19).
Methods: Adults without prior 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 consecutively) or placebo. Primary endpoints 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: 1121 participants were randomized and dosed (mean age 46 years; 49% females; 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 162/749 (21.6%) and 111/372 (29.8%) participants with AZD7442 and placebo, respectively, mostly mild/moderate. RT-PCR-positive symptomatic COVID-19 occurred in 23/749 (3.1%) and 17/372 (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) versus placebo.
Conclusions: This study did not meet the primary efficacy endpoint of post-exposure prevention of symptomatic COVID-19 with AZD7442 versus placebo. However, predefined 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.
Keywords: AZD7442; COVID-19; SARS-CoV-2; monoclonal antibodies; post-exposure prophylaxis.