Evaluation of the safety and efficacy of XAV-19 in patients with COVID-19-induced moderate pneumonia: study protocol for a randomized, double-blinded, placebo-controlled phase 2 (2a and 2b) trial.

Abstract

BACKGROUND:

Early inhibition of entry and replication of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a very promising therapeutic approach. Polyclonal neutralizing antibodies offers many advantages such as providing immediate immunity, consequently blunting an early pro-inflammatory pathogenic endogenous antibody response and lack of drug-drug interactions. By providing immediate immunity and inhibiting entry into cells, neutralizing antibody treatment is of interest for patient with COVID-19-induced moderate pneumonia. Convalescent plasma to treat infected patients is therefore a relevant therapeutic option currently under assessment (CORIMUNO-PLASM NCT04324047). However, the difficulties of collecting plasma on the long term are not adapted to a broad use across all populations. New polyclonal humanized anti-SARS-CoV2 antibodies (XAV-19) developed by Xenothera and administered intravenous. XAV-19 is a heterologous swine glyco-humanized polyclonal antibody (GH-pAb) raised against the spike protein of SARS-CoV-2, blocking infection of ACE-2-positive human cells with SARS-CoV-2.

METHODS:

Pharmacokinetic and pharmacodynamic studies have been performed in preclinical models including primates. A first human study with another fully representative GH-pAb from Xenothera is ongoing in recipients of a kidney graft. These studies indicated that 5 consecutive administrations of GH-pAbs can be safely performed in humans. The objectives of this 2-step phase 2 randomized double-blinded, placebo-controlled study are to define the safety and the optimal XAV-19 dose to administrate to patients with SARS-CoV-2 induced moderate pneumonia, and to assess the clinical benefits of a selected dose of XAV-19 in this population.

DISCUSSION:

This study will determine the clinical benefits of XAV-19 when administered to patients with SARS-CoV-2-induced moderate pneumonia. As a prerequisite, a first step of the study will define the safety and the dose of XAV-19 to be used. Such treatment might become a new therapeutic option to provide an effective treatment for COVID-19 patients (possibly in combination with anti-viral and immunotherapies). Further studies could later evaluate such passive immunotherapy as a potential post-exposure prophylaxis.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT04453384 , registered on 1 July 2020, and EUDRACT 2020-002574-27, registered 6 June 2020.

• Authors: Benjamin Gaborit, Bernard Vanhove, Marie-Anne Vibet, Aurélie Le Thuaut, Karine Lacombe, Vincent Dubee, Florence Ader, Virginie Ferre, Eric Vicaut, Jéremie Orain, Morgane Le Bras, Anne Omnes, Laetitia Berly, Alexandra Jobert, Pascale Morineau-Le Houssine, Karine Botturi, Régis Josien, Laurent Flet, Nicolas Degauque, Sophie Brouard, Odile Duvaux, Alexandra Poinas, François Raffi, POLYCOR study group
• Journal: Trials (Trials) Vol. 22 Issue 1 Pg. 199 (Mar 09 2021) ISSN: 1745-6215 [Electronic] England
• PMID: 33750432 (Publication Type: Clinical Trial Protocol, Journal Article)

Chemical References

• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing
• Immunoglobulin G
• Spike Glycoprotein, Coronavirus
• spike protein, SARS-CoV-2

Topics

• Animals
• Antibodies, Monoclonal, Humanized
• Antibodies, Neutralizing (therapeutic use)
• COVID-19 (therapy)
• Clinical Trials, Phase II as Topic
• Double-Blind Method
• Humans
• Immunization, Passive
• Immunoglobulin G (therapeutic use)
• Oxygen Inhalation Therapy
• Randomized Controlled Trials as Topic
• SARS-CoV-2 (immunology)
• Severity of Illness Index
• Spike Glycoprotein, Coronavirus (immunology)
• Swine
• Time Factors
• COVID-19 Serotherapy