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. 2021 Mar 9;22(1):199.
doi: 10.1186/s13063-021-05132-9.

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  1   2 , Bernard Vanhove  3 , Marie-Anne Vibet  4 , Aurélie Le Thuaut  4 , Karine Lacombe  5 , Vincent Dubee  6 , Florence Ader  7   8 , Virginie Ferre  2   9 , Eric Vicaut  10 , Jéremie Orain  1   2 , Morgane Le Bras  1   2 , Anne Omnes  4 , Laetitia Berly  4 , Alexandra Jobert  4 , Pascale Morineau-Le Houssine  1   2 , Karine Botturi  11 , Régis Josien  12   13 , Laurent Flet  14 , Nicolas Degauque  12   15 , Sophie Brouard  12   15 , Odile Duvaux  3 , Alexandra Poinas  16 , François Raffi  1   2 ; POLYCOR study group
Collaborators, Affiliations

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 et al. Trials. .

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.

PubMed Disclaimer

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
See this image and copyright information in PMC

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