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

Background: We assessed the pharmacokinetics and safety of XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2, in COVID-19-related moderate pneumonia. In vitro, 100% neutralization activity is seen with XAV-19 concentrations above 5 microg/mL. Methods: In this phase 2a trial, adults with COVID-19-related moderate pneumonia of ≤10 days duration were randomized to infusion of XAV-19 0.5 mg/kg at day 1 and day 5 (group 1), 2 mg/kg at day 1 and day 5 (group 2), 2 mg/kg at day 1 (group 3) or placebo. Results: 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, XAV-19 serum concentrations (microg/mL, median, range) at Cmax and at day 8 were 9.1 (5.2-18.1) and 6.4 (2.8-11.9), 71.5 and 47.2, and 50.4 (29.1-55.0) and 20.3 (12.0-22.7) for groups 1, 2 and 3, respectively (p=0.012). Terminal half-life (median, range) was estimated at 11.4 (5.5-13.9) days for 2 mg/kg of XAV-19 at day 1. Serum XAV-19 concentrations were above the target concentration of 10 microg/mL (tow fold the in vitro 100% inhibitory concentration [IC100]) from the end of perfusion to more than 8 days for XAV-19 2 mg/kg at day 1. No hypersensitivity or infusion-related reactions were reported during treatment, there was no discontinuation for adverse events and no serious adverse events related to study drug. Conclusions: Single intravenous dose of 2 mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability.

A Polyclonal Antibody Dosing Strategy to Reduce the Viral Load of Multiple Coronavirus Mutants in COVID-19 Patients with Pneumonia

“…To this end, a clinical study was conducted in human subjects for XAV-19. Specifically, the concentration vs. time and effect vs. time profiles were reported for the drug in COVID-19 patients with moderate pneumonia [1]. In this study, an intravenous dose of 2 mg/kg was deemed safe, and it showed beneficial effect.…”

“…Specifically, XAV-19 has a half-life of 11.2 days, which allows maintenance of effective concentrations for a few weeks. This value, estimated by Gaborit et al [1] was used to determine the elimination rate constant for XAV-19 (Table 2). Table 2 shows the other parameters used to fit the pharmacokinetic and pharmacodynamic data.…”

“…There are several limitations to this study. Drug concentrations reported in the source article [1] as mean values and drug effects reported as median values were used in this study. The model was fit to these mean/median concentrations and did not account for the variability in the data.…”

“…1 Serum concentrations of XAV-19 polyclonal antibody following single intravenous infusion at a dose of 2 mg/kg. Based on Gaborit et al [1].…”

High-dose immunoglobulins from convalescent donors for patients hospitalised with COVID-19

“…Many studies investigating hIVIG for COVID-19 are ongoing. The few published studies vary substantially in their setup, such as the characteristics of the studied intervention being non-human in origin (eg, horse or swine IgG) 10 , 11 or human-derived hIVIG. 12 , 13 Studies so far have been small—ranging from 18 to 245 participants—making interpretation of their results challenging.…”