Pharmacokinetics of the Monoclonal Antibody, Sotrovimab, in Healthy Participants Following IM Administration at Different Injection Sites

Abstract

Sotrovimab is a recombinant human monoclonal antibody for the early treatment of mild‐to‐moderate COVID‐ 19. A phase I, open‐label, randomized, parallel‐group study was conducted to investigate the pharmacokinetics, relative bioavailability, safety, and tolerability of two concentrations of sotrovimab administered intramuscularly at different injection sites in healthy volunteers. The study consisted of three parts (A, B, and C) and the pharmacokinetic results from Part A are reported herein. In Part A, participants were randomized in a 2:2:1:1 ratio to a 500 mg dose of 62.5 mg/mL sotrovimab administered into dorsogluteal muscle, or 100 mg/mL sotrovimab administered into dorsogluteal, anterolateral thigh, or deltoid muscles. Formulation concentration did not impact exposure following dorsogluteal administration; the point estimates (90% confidence interval [CI]) of the geometric mean ratios (GMRs) of area under the curve (AUC)inf and maximum serum concentration (Cmax) for dorsogluteal administration of 100 mg/mL vs. 62.5 mg/mL intramuscular sotrovimab were 0.95 (0.86–1.05) and 1.14 (1.02–1.27), respectively. However, the administration of 100 mg/mL sotrovimab in thigh or deltoid resulted in increased exposure relative to gluteal injections; the point estimates (90% CI) of the GMRs for 100 mg/mL intramuscular sotrovimab administered into thigh or deltoid muscles vs. 100 mg/mL administered dorsogluteally were 1.63 (1.46–1.83) and 1.50 (1.34–1.67) for AUCinf, and 1.82 (1.60–2.08) and 1.49 (1.31–1.69) for Cmax, respectively. Notably, thigh and deltoid administration also resulted in lower variability in key pharmacokinetic parameters such as AUC, Cmax, apparent clearance and volume of distribution, and earlier achievement of Cmax, than dorsogluteal intramuscular administration of sotrovimab.