Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial
Adrienne E Shapiro, Elias Sarkis, Jude Acloque, Almena Free, Yaneicy Gonzalez-Rojas, Rubaba Hussain, Erick Juarez, Jaynier Moya, Naval Parikh, David Inman, Deborah Cebrik, Ahmed Nader, Nadia Noormohamed, Qianwen Wang, Andrew Skingsley, Daren Austin, Amanda Peppercorn, Maria L Agostini, Sergio Parra, Sophia Chow, Erik Mogalian, Phillip S Pang, David K Hong, Jennifer E Sager, Wendy W Yeh, Vir Biotechnology, Inc Elizabeth L Alexander, Dr Leah A Gaffney, Dr Anita Kohli
doi:10.1101/2023.03.21.23287410
Sotrovimab 500-mg IM was non-inferior to sotrovimab 500-mg IV for treatment of mild/moderate COVID-19 in high-risk patients, measured by all-cause hospitalization >24h or death through day 29, and was well-tolerated. Sotrovimab IM should provide easier outpatient access to COVID-19 treatment.
Funding The study was supported by Vir Biotechnology, Inc. in collaboration with GSK.
Author Contributions PSP, DKH, EA, WWY, EM, JES, DA, SC, and AP conceptualized and designed the study. All authors acquired, analyzed and/or interpreted the data. DI and DC conducted the statistical analyses. AK, LAG, and DI accessed and verified the data. All authors drafted the manuscript and critically reviewed and revised the manuscript for important intellectual content. All authors had full access to all the data in the study, take responsibility for the accuracy of the analysis, and had authority over manuscript preparation and the decision to submit the manuscript for publication.
Conflict of Interest Disclosures
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doi:10.1101/2023.01.20.23284849DOI record:
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"abstract": "<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This phase 3, randomized, multicenter, open-label study tested non-inferiority of IM to IV administration using a 3.5% absolute non-inferiority margin. From June to August 2021, patients aged ≥12 years with COVID-19, not hospitalized or receiving supplemental oxygen, and at high risk for progression were randomized 1:1:1 to a single 500-mg IV sotrovimab infusion or 500-mg or 250-mg IM sotrovimab injection. The primary composite endpoint was progression to all-cause hospitalization for >24 hours for acute management of illness or all-cause death through day 29.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Sotrovimab 500 mg IM was non-inferior to 500 mg IV: 10/376 (2.7%) participants in the sotrovimab 500-mg IM group versus 5/378 (1.3%) in the sotrovimab 500-mg IV group met the primary endpoint (absolute adjusted risk difference: 1.06% [95% confidence interval [CI]: −1.15%, 3.26%]). The CI upper limit was lower than the prespecified non-inferiority margin of 3.5%. 250-mg IM group enrollment was discontinued early because a greater proportion of hospitalizations was seen in that group versus the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease related events and died (500 mg IM: 2/393 [<1%]; 250 mg IM: 2/195 [1%]).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Sotrovimab 500-mg IM injection was well tolerated and non-inferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.</jats:p></jats:sec><jats:sec><jats:title>Registration</jats:title><jats:p><jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"uri\" xlink:href=\"http://ClinicalTrials.gov\">ClinicalTrials.gov</jats:ext-link>Identifier:<jats:ext-link xmlns:xlink=\"http://www.w3.org/1999/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT04913675\">NCT04913675</jats:ext-link></jats:p></jats:sec><jats:sec><jats:title>Key Points</jats:title><jats:p>Sotrovimab 500-mg IM was non-inferior to sotrovimab 500-mg IV for treatment of mild/moderate COVID-19 in high-risk patients, measured by all-cause hospitalization >24h or death through day 29, and was well-tolerated. Sotrovimab IM should provide easier outpatient access to COVID-19 treatment.</jats:p></jats:sec>",
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