Benjamin Gaborit1,2, Bernard Vanhove3, Marie-Anne Vibet4, Aurélie Le Thuaut4, Karine Lacombe5, Vincent Dubee6, Florence Ader7,8, Virginie Ferre2,9, Eric Vicaut10, Jéremie Orain1,2, Morgane Le Bras1,2, Anne Omnes4, Laetitia Berly4, Alexandra Jobert4, Pascale Morineau-Le Houssine1,2, Karine Botturi11, Régis Josien12,13, Laurent Flet14, Nicolas Degauque12,15, Sophie Brouard12,15, Odile Duvaux3, Alexandra Poinas16, François Raffi1,2. 1. CHU Nantes, Department of Infectious Disease, Clinical Investigation, Nantes, France. 2. CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France. 3. Xenothera, Nantes, France. 4. CHU Nantes, Sponsor Department, Nantes, France. 5. Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, INSERM, AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et Tropicales, Paris, France. 6. CHU Angers, Service de Maladies Infectieuses et Tropicales, Angers, France. 7. Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Université Lyon, F-69007, Lyon, France. 8. Département des Maladies infectieuses et tropicales, Hospices Civils de Lyon, F-69004, Lyon, France. 9. CHU Nantes, Virology Laboratory, Nantes, France. 10. APHP, Department of Biostatistics, Université Paris-Diderot, Sorbonne-Paris Cité, Fernand Widal Hospital, Paris, France. 11. CHU Nantes, Partnership and Innovation Department, Nantes, France. 12. Nantes Université, CHU Nantes, Inserm, Centre de Recherche en Transplantation et Immunologie, UMR 1064, ITUN, F-44000, Nantes, France. 13. CHU Nantes, Laboratoire d'Immunologie, Nantes, France. 14. CHU Nantes, Pharmacy Department, Nantes, France. 15. CHU Nantes, Nantes Université, Institut de Transplantation Urologie Néphrologie (ITUN), Nantes, France. 16. CHU Nantes and Inserm, Clinical Investigation Centre CIC1413, Nantes, France. Alexandra.poinas@chu-nantes.fr.
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.
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: William R Strohl; Zhiqiang Ku; Zhiqiang An; Stephen F Carroll; Bruce A Keyt; Lila M Strohl Journal: BioDrugs Date: 2022-04-27 Impact factor: 7.744
Authors: Stephen Findlay-Wilson; Linda Easterbrook; Sandra Smith; Neville Pope; Gareth Humphries; Holger Schuhmann; Didier Ngabo; Emma Rayner; Ashley David Otter; Tom Coleman; Bethany Hicks; Victoria Anne Graham; Rachel Halkerston; Kostis Apostolakis; Stephen Taylor; Susan Fotheringham; Amanda Horton; Julia Anne Tree; Matthew Wand; Roger Hewson; Stuart David Dowall Journal: Antiviral Res Date: 2022-05-06 Impact factor: 10.103
Authors: Bernard Vanhove; Stéphane Marot; Ray T So; Benjamin Gaborit; Gwénaëlle Evanno; Isabelle Malet; Guillaume Lafrogne; Edwige Mevel; Carine Ciron; Pierre-Joseph Royer; Elsa Lheriteau; François Raffi; Roberto Bruzzone; Chris Ka Pun Mok; Odile Duvaux; Anne-Geneviève Marcelin; Vincent Calvez Journal: Front Immunol Date: 2021-11-15 Impact factor: 7.561
Authors: Benjamin Gaborit; Eric Dailly; Bernard Vanhove; Régis Josien; Karine Lacombe; Vincent Dubee; Virginie Ferre; Sophie Brouard; Florence Ader; Marie-Anne Vibet; Aurélie Le Thuaut; Richard Danger; Laurent Flet; Anne Omnes; Laetitia Berly; Anne Chiffoleau; Alexandra Jobert; Odile Duvaux; François Raffi Journal: Antimicrob Agents Chemother Date: 2021-08-17 Impact factor: 5.191