Article
作者: Inman, David ; Chow, Sophia ; Gonzalez-Rojas, Yaneicy ; Yeh, Wendy W ; Sager, Jennifer E ; Wang, Qianwen ; Skingsley, Andrew ; Shapiro, Adrienne E ; Hussain, Rubaba ; Gaffney, Leah A ; Moya, Jaynier ; Pang, Phillip S ; Hong, David K ; Kohli, Anita ; Parikh, Naval ; Alexander, Elizabeth L ; Cebrik, Deborah ; Acloque, Jude ; Free, Almena ; Noormohamed, Nadia ; Austin, Daren ; Nader, Ahmed ; Peppercorn, Amanda ; Juarez, Erick ; Agostini, Maria L ; Mogalian, Erik ; Sarkis, Elias ; Parra, Sergio
Background: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.
Method:This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.5%. From June to August 2021, patients aged ≥12 years with COVID-19, who were neither hospitalized nor receiving supplemental oxygen but were at high risk for progression, were randomized 1:1:1 to receive sotrovimab as a single 500-mg IV infusion or a 500- or 250-mg IM injection. The primary composite endpoint was progression to (1) all-cause hospitalization for >24 hours for acute management of illness or (2) all-cause death through day 29.
Results:Sotrovimab 500 mg IM was noninferior to 500 mg IV: 10 (2.7%) of 376 participants vs 5 (1.3%) of 378 met the primary endpoint, respectively (absolute adjusted risk difference, 1.06%; 95% CI, −1.15% to 3.26%). The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. The 250-mg IM group was discontinued early because of the greater proportion of hospitalizations vs 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%).
Conclusions:Sotrovimab 500-mg IM injection was well tolerated and noninferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
Clinical Trials Registration:ClinicalTrials.gov: NCT04913675.