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

Trials

POLYCOR study group¹  Eric Vicaut²  Vincent Dubee³  Alexandra Poinas⁴  Virginie Ferre⁴  Pascale Morineau-Le Houssine⁵  Morgane Le Bras⁵  Jéremie Orain⁵  Benjamin Gaborit⁵  François Raffi⁵  Karine Botturi⁶  Laurent Flet⁷  Aurélie Le Thuaut⁸  Anne Omnes⁸  Marie-Anne Vibet⁸  Alexandra Jobert⁸  Laetitia Berly⁸  Florence Ader⁹  Karine Lacombe^1,10  Nicolas Degauque^1,11  Sophie Brouard^1,11  Régis Josien^1,11  Odile Duvaux^1,12  Bernard Vanhove^1,12 

[1] ;APHP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital;CHU Angers, Service de Maladies Infectieuses et Tropicales;CHU Nantes and Inserm, Clinical Investigation Centre CIC1413;CHU Nantes, Department of Infectious Disease, Clinical Investigation;CHU Nantes, Partnership and Innovation Department;CHU Nantes, Pharmacy Department;CHU Nantes, Sponsor Department;Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon;Institut Pierre Louis d’Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et Tropicales;Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN;Xenothera;

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

DOI  :  10.1186/s13063-021-05132-9

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown