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

  1. Benjamin Gaborit
  2. Eric Dailly
  3. Bernard Vanhove
  4. Régis Josien
  5. Karine Lacombe
  6. Vincent Dubee
  7. Virginie Ferre
  8. Sophie Brouard
  9. Florence Ader
  10. Marie-Anne Vibet
  11. Aurélie Le Thuaut
  12. Richard Danger
  13. Laurent Flet
  14. Anne Omnes
  15. Laetitia Berly
  16. Anne Chiffoleau
  17. Alexandra Jobert
  18. Odile Duvaux
  19. François Raffi
  20. POLYCOR trial group
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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 μg/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 (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 [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.

Trial registration

ClinicalTrials.gov Identifier: <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT04453384">NCT04453384</ext-link>

Main point

In this first-in-human trial including patients with COVID-19-related pneumonia, a single 2mg/kg dose of a swine glyco-humanized polyclonal anti-SARS-CoV-2 antibody, achieved serum concentrations above the target of neutralization threshold for 8 days in all patients, with good tolerability and safety.

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