AZD7442 (Tixagevimab/Cilgavimab) for Post-Exposure Prophylaxis of Symptomatic Coronavirus Disease 2019
MD Myron J Levin, MD Andrew Ustianowski, MSc Steven Thomas, PhD Alison Templeton, PhD Yuan Yuan, PhD Seth Seegobin, PhD Catherine F Houlihan, MD Ibrahim Menendez-Perez, MBBS Simon Pollett, PhD Rosalinda H Arends, PhD Rohini Beavon, MSc Kanika Dey, MD Pedro Garbes, PhD Elizabeth J Kelly, PhD Gavin C K W Koh, MD Stefan Ivanov, MD Karen A Near, PhD Audrey Sharbaugh, PhD Katie Streicher, PhD Menelas N Pangalos, PhD Mark T Esser
Clinical Infectious Diseases, doi:10.1093/cid/ciac899
Background: We report primary results of a phase 3 trial of AZD7442 (tixagevimab/cilgavimab) for post-exposure prophylaxis to prevent symptomatic coronavirus disease 2019 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.
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'abstract': '<jats:title>Abstract</jats:title>\n'
' <jats:sec>\n'
' <jats:title>Background</jats:title>\n'
' <jats:p>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)</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Methods</jats:title>\n'
' <jats:p>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.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Results</jats:title>\n'
' <jats:p>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.</jats:p>\n'
' </jats:sec>\n'
' <jats:sec>\n'
' <jats:title>Conclusions</jats:title>\n'
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'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.</jats:p>\n'
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