Abstract
BACKGROUND AND OBJECTIVES: The emergence of severe acute respiratory syndrome coronavirus 2 variants against which sotrovimab has lower in vitro neutralisation activity has led to the exploration of higher (> 500-mg intravenous) doses. This study evaluated the safety, tolerability and pharmacokinetics of intravenous sotrovimab 3000 mg. METHODS: We conducted a phase I, open-label, single-arm study in healthy adults. Participants were administered a single 3000-mg dose of intravenous sotrovimab (100 mg/mL) over 60 min (50 mg/min). Adverse events, serious adverse events and adverse events of special interest were assessed through week 35. Sotrovimab pharmacokinetics were evaluated through week 24. RESULTS: Of 100 participants enrolled, 98 received sotrovimab (median age 42.5 [range 18-64] years; 52% male; mean body mass index 25.25 kg/m(2)) and 96 completed the study. Overall, 37% (n = 36/98) of the participants reported adverse events, five of which were considered to be treatment related. The most common type of event was infection (13%; n = 13/98) with upper respiratory tract infection (9%; n = 9/98) being frequent. Two Grade 1 adverse events of special interest were reported. There were no serious adverse events, deaths or adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for this dose of sotrovimab, assuming linear dose-proportional pharmacokinetics, based on the population pharmacokinetic model of sotrovimab. CONCLUSIONS: Intravenous sotrovimab 3000 mg, administered over 60 min, was generally well tolerated by healthy volunteers, with a low incidence of adverse events and adverse events of special interest, no documented serious adverse events and no adverse events leading to discontinuation. Pharmacokinetic results were in line with expectations for a 3000-mg dose, assuming linear dose-proportional pharmacokinetics. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT05280717; date of registration 4 March, 2022.