Intramuscular Versus Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Non-inferiority Clinical Trial

DOI record: { "DOI": "10.1101/2023.03.21.23287410", "URL": "http://dx.doi.org/10.1101/2023.03.21.23287410", "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 &gt;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 &lt;1% to 2% of participants across groups. Four participants experienced serious disease related events and died (500 mg IM: 2/393 [&lt;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 &gt;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>", "accepted": { "date-parts": [ [ 2023, 3, 24 ] ] }, "author": [ { "ORCID": "http://orcid.org/0000-0002-3106-1258", "affiliation": [], "authenticated-orcid": false, "family": "Shapiro", "given": "Adrienne E.", "sequence": "first" }, { "affiliation": [], "family": "Sarkis", "given": "Elias", "sequence": "additional" }, { "affiliation": [], "family": "Acloque", "given": "Jude", "sequence": "additional" }, { "affiliation": [], "family": "Free", "given": "Almena", "sequence": "additional" }, { "affiliation": [], "family": "Gonzalez-Rojas", "given": "Yaneicy", "sequence": "additional" }, { "affiliation": [], "family": "Hussain", "given": "Rubaba", "sequence": "additional" }, { "affiliation": [], "family": "Juarez", "given": "Erick", "sequence": "additional" }, { "affiliation": [], "family": "Moya", "given": "Jaynier", "sequence": "additional" }, { "affiliation": [], "family": "Parikh", "given": 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