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

Objective: 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. To evaluate the optimal dose and safety of XAV-19 during this first administration to patients with COVID-19-related moderate pneumonia. Methods : In this phase 2a trial, adults with COVID-19-related moderate pneumonia of ≤10 days duration were randomized to infusion of XAV-19 0.5mg/kg at day 1 and day 5 (group 1), 2mg/kg at day 1 and day 5 (group 2), 2mg/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 (μg/mL, median, range) at C max 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 μg/mL (tow fold the in vitro 100% inhibitory concentration [IC 100 ]) 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 2mg/kg of XAV-19 demonstrated high serum concentrations, predictive of potent durable neutralizing activity with good tolerability. Trial registration: ClinicalTrials.gov Identifier: NCT04453384

Antibody and cellular therapies for treatment of covid-19: a living systematic review and network meta-analysis

“…The supplementary data present the assessment of risk of bias of the included studies for each outcome. Twelve trials5054566065677286 proved at low risk of bias for all domains. All other studies proved at probably high or high risk of bias for at least one domain.…”

“…After screening 52350 titles and abstracts and 1029 full texts, 47 unique randomised controlled trials that evaluated antiviral antibody or cellular treatments were identified as of 21 July 2021 (fig 1). 43444546474849505152535455565758596061626364656667686970717273747576777879808182838485868788 A table of excluded full texts is provided in the supplementary data on bmj.com. Searches of living evidence retrieval services identified 11 publications of eligible randomised trials, which were reconciled with our formal search strategy when necessary 222324254549566466676875838688.…”

“…43444546474849505152535455565758596061626364656667686970717273747576777879808182838485868788 A table of excluded full texts is provided in the supplementary data on bmj.com. Searches of living evidence retrieval services identified 11 publications of eligible randomised trials, which were reconciled with our formal search strategy when necessary 222324254549566466676875838688. Thirty randomised controlled trials were published in a peer reviewed journal, 16 were preprints, and one was an abstract.…”

XAV-19, a swine glyco-humanized polyclonal antibody against SARS-CoV-2 Spike receptor-binding domain, targets multiple epitopes and broadly neutralizes variants

“…Third, polyclonal antibodies produced in their Fab'2 format from horses 21 or in their IgG format from humanized cows 22 or glyco-humanized pigs 23 have also proven efficacy to neutralize SARS-CoV-2. The safety and tolerability in humans of Fab'2 from horses and of humanized IgG polyclonal antibodies has been confirmed recently in different clinical trials (Lopardo et al, 2021 21 , NCT04453384, NCT04469179, Gaborit et al, 2021 24 ), contrasting with unmodified polyclonal antibodies containing wild-type IgG antibodies that induce serum sickness and allergic reactions (including fever and skin rashes) in 20 to 30% of the patients, excepting for those who concomitantly receive immunosuppression and high doses steroids 25,26 . A partial efficacy of anti-SARS-CoV-2 Fab'2 from horses has been reported in those patients with negative baseline antibodies (NCT04494984).…”

“…Early after Covid-19 outbreak onset, many labs have been able to rapidly develop neutralizing antibodies. One year later, as of mid-2021, more than 93 clinical trials assessing the safety and benefit of mAbs and 8 of polyclonal antibodies are listed in the Clinicaltrials.gov repository ) estimated at 11.4 days24,46 . The data presented here, together with these pharmacokinetic data, indicate that XAV-19 can provide high and sustained therapeutic activity in vivo.…”