Safety, Virology, Pharmacokinetics, and Clinical Experience of High-Dose Intravenous Sotrovimab for the Treatment of Mild to Moderate COVID-19: An Open-Label Clinical Trial.

Background: Five hundred milligrams of intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression.
Methods: This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary end point was the occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through day 8. Safety, pharmacokinetics, viral load, and hospitalization >24 hours for acute management of illness or death through day 29 were assessed.
Results: All participants (n = 81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n = 2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9 µg/mL. Viral load decreased from baseline through day 29; only 2 (3%) participants had a persistently high viral load (≥4.1 log ₁₀ copies/mL) at day 8.
Conclusions: Two thousand milligrams of IV sotrovimab was well tolerated, with no safety signals observed.
Trial Registration: ClinicalTrials.gov Identifier: NCT04913675.
Competing Interests: Potential conflicts of interest. S.P., M.T., G.S., A.E.-Z., J.S., M.A., and E.A. are employees of Vir Biotechnology, Inc. and report stock ownership in Vir Biotechnology, Inc. and third-party funding from GSK to Vir Biotechnology, Inc. for the submitted work. S.S., C.X., and A.S. are employees of GSK and report stock ownership in GSK. J.M., E.J., R.H.-L., J.M.G., J.D., R.H., and G.A. report acting as a trial investigator for Vir Biotechnology, Inc. and receiving nonfinancial support from Vir Biotechnology, Inc. during the conduct of the study.
(© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)