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 days were randomized to receive an infusion of XAV-19 at 0.5 mg/kg of body weight at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), or 2 mg/kg at day 1 (group 3) or placebo. Eighteen patients ( n = 7 for group 1, n = 1 for group 2, n = 5 for group 3, and n = 5 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 ( C max ) 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 = 0.012). The median terminal half-life (range) was estimated at 11.4 (5.5 to 13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 μg/ml (2-fold the in vitro 100% inhibitory concentration [IC 100 ]) from the end of perfusion to more than 8 days for XAV-19 at 2 mg/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 mg/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 .).
Keywords: COVID-19; XAV-19; phase IIa; pneumonia; polyclonal glyco-humanized anti-SARS-CoV-2 antibody.
【저자키워드】 COVID-19, Pneumonia, breath, XAV-19, phase IIa, polyclonal glyco-humanized anti-SARS-CoV-2 antibody., 【초록키워드】 Treatment, coronavirus disease, SARS-CoV-2, Coronavirus disease 2019, coronavirus, Trial, antibody, body weight, pharmacokinetics, drug, in vitro, severe acute respiratory syndrome Coronavirus, adverse events, Randomized, serum, Neutralizing activity, Characteristics, anti-SARS-CoV-2 antibody, adverse event, Patient, Placebo, group, moderate, Perfusion, infusion, administration, Concentration, phase IIa, hypersensitivity, Predictive, during treatment, polyclonal antibody, Serious Adverse Events, Serious Adverse Event, acute respiratory syndrome, Tolerability, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, reaction, baseline characteristics, study drug, Registered, optimal dose, serum concentrations, C max, inhibitory concentration, concentrations, polyclonal, maximum serum concentration, enrolled, evaluate, reported, median, demonstrated, receive, IIa, intravenous dose, 【제목키워드】 Safety, phase, IIa,