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

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, Eric Dailly, Thomas Guimard, Cécile Braudeau, Denis Malvy, Jean-François Faucher, Gabriela Illes Hajnal, Marc-Olivier Vareil, Mariam Roncato-Saberam, Laurent Vacher, Charlotte Biron, Maeva Lefebvre, Géraldine Gallot, Paul Le Turnier, Colin Deschanvres, Raphael Lecomte, Marie Chauveau, Anne-Sophie Lecompte, Matthieu Grégoire, Ronan Bellouard, Guillaume Deslandes, Zineb Ouazene, Diane Bollens, Thibault Chiarabani, Jessica Krause-Le Garrec, Agathe Becker, Pierre Chauvelot, Anne Conrad, Tristan Ferry, Patrick Miailhes, Cécile Pouderoux, Sandrine Roux, Claire Triffault-Fillit, 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, Eric Dailly, Thomas Guimard, Cécile Braudeau, Denis Malvy, Jean-François Faucher, Gabriela Illes Hajnal, Marc-Olivier Vareil, Mariam Roncato-Saberam, Laurent Vacher, Charlotte Biron, Maeva Lefebvre, Géraldine Gallot, Paul Le Turnier, Colin Deschanvres, Raphael Lecomte, Marie Chauveau, Anne-Sophie Lecompte, Matthieu Grégoire, Ronan Bellouard, Guillaume Deslandes, Zineb Ouazene, Diane Bollens, Thibault Chiarabani, Jessica Krause-Le Garrec, Agathe Becker, Pierre Chauvelot, Anne Conrad, Tristan Ferry, Patrick Miailhes, Cécile Pouderoux, Sandrine Roux, Claire Triffault-Fillit

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.

Keywords: Anti-SARS-CoV-2 antibodies; COVID-19; Immunotherapy; Moderate pneumonia; Phase 2; Randomized controlled trial.

Conflict of interest statement

FR has received consultancy fees from Gilead Sciences and Xenothera. OD and BV are employees and shareholders of Xenothera.

Figures

Fig. 1
Fig. 1
Diagram of phase 2a study. a Phase2a—group1. b Phase 2b—group 2
Fig. 2
Fig. 2
Diagram of phase 2b study
Fig. 3
Fig. 3
Study schedule for phase2a and phase 2b

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