Pharmacokinetics and Safety of XAV-19, a Swine Glyco-humanized Polyclonal Anti-SARS-CoV-2 Antibody, for COVID-19-Related Moderate Pneumonia: a Randomized, Double-Blind, Placebo-Controlled, Phase IIa Study

Abstract

We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in coronavirus disease 2019 (COVID-19)-related moderate pneumonia. The objective was to evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. ABSTRACT We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in coronavirus disease 2019 (COVID-19)-related moderate pneumonia. The objective was to evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. In this phase IIa trial, adults with COVID-19-related moderate pneumonia with a duration of ≤10\u2009days were randomized to receive an infusion of XAV-19 at 0.5\u2009mg/kg of body weight at day 1 and day 5 (group 1), 2\u2009mg/kg at day 1 and day 5 (group 2), or 2\u2009mg/kg at day 1 (group 3) or placebo. Eighteen patients (n\u2009=\u20097 for group 1, n\u2009=\u20091 for group 2, n\u2009=\u20095 for group 3, and n\u2009=\u20095 for placebo) were enrolled. Baseline characteristics were similar across groups; median XAV-19 serum concentrations (ranges) at the time of the maximum serum concentration of the drug (Cmax) and at day 8 were 9.1 (5.2 to 18.1) and 6.4 (2.8 to 11.9) μg/ml, 71.5 and 47.2 μg/ml, and 50.4 (29.1 to 55.0) and 20.3 (12.0 to 22.7) μg/ml for groups 1, 2, and 3, respectively (P\u2009=\u20090.012). The median terminal half-life (range) was estimated at 11.4 (5.5 to 13.9) days for 2\u2009mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10\u2009μg/ml (2-fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8\u2009days for XAV-19 at 2\u2009mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, and there were no discontinuations for adverse events and no serious adverse events related to the study drug. A single intravenous dose of 2\u2009mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. (This study has been registered at ClinicalTrials.gov under identifier NCT04453384.)