Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial

Benjamin Gaborit; Bernard Vanhove; Karine Lacombe; Thomas Guimard; Laurent Hocqueloux; Ludivine Perrier; Vincent Dubee; Virginie Ferre; Celine Bressollette; Régis Josien; Aurélie Le Thuaut; Marie-Anne Vibet; Alexandra Jobert; Eric Dailly; Florence Ader; Sophie Brouard; Odile Duvaux; François Raffi; POLYCOR study group

doi:10.1093/ofid/ofad525

Effect of Swine Glyco-humanized Polyclonal Neutralizing Antibody on Survival and Respiratory Failure in Patients Hospitalized With Severe COVID-19: A Randomized, Placebo-Controlled Trial

Open Forum Infect Dis. 2023 Oct 20;10(11):ofad525. doi: 10.1093/ofid/ofad525. eCollection 2023 Nov.

Authors

Benjamin Gaborit^{1

2}, Bernard Vanhove³, Karine Lacombe⁴, Thomas Guimard⁵, Laurent Hocqueloux⁶, Ludivine Perrier⁷, Vincent Dubee^{8

9}, Virginie Ferre¹⁰, Celine Bressollette¹⁰, Régis Josien^{2

11}, Aurélie Le Thuaut^{7

12}, Marie-Anne Vibet^{7

12}, Alexandra Jobert^{7

13}, Eric Dailly¹⁴, Florence Ader^{15

16}, Sophie Brouard², Odile Duvaux³, François Raffi¹; POLYCOR study group

Collaborators

POLYCOR study group:
Benjamin Gaborit, François Raffi, Maeva Lefebvre, Charlotte Biron, Raphaël Lecomte, Cécile Braudeau, Marie Chauveau, Eric Dailly, Colin Deschanvres, Matthieu Gregoire, Anne-Sophie Lecomte, Laurent Flet, Martine Tching-Sin, Eugenie Clapeau, Jérémie Orain, Morgane Le Bras, Alexandre Duval, Isabelle Portier, Clara Mora, Anne-Sophie Boureau, Etienne Seronie-Doutriaux, Agnès Rouaud, Pamela Hublain, Laurence Le Jumeau De Kergaradec, Carole Agasse, Vivien Danielo, Megguy Bernard, Régine Valero, Karine Lacombe, Diane Bollens, Thibault Chiarabini, Nadia Valin, Patrick Ingiliz, Zineb Ouazene, Bénédicte Lefebvre, François Lecardonnel, Christian Tran, Raynald Feliho, Manuela Le Cam, Julie Lamarque, Jean-Luc Lagneau, Cyrielle Letaillandier, Anne Daguenel-Nguyen, Clémentine Mayala-Kanda, Djeneba Fofana, Arianna Fiorentino, Thomas Guimard, Yves Bleher, Jean-Luc Esnault, Dominique Merrien, Blandine Le Claire, Marine Morrier, Delphine Boucher, Romain Lamberet, Clémentine Coudon, Romain Decours, Hélène Durand, Armelle Pegeot, Edwige Migne, Hélène Pelerin, Yannick Poirier, Laurent Hocqueloux, Thierry Prazuck, Barbara De Dieuleveult, Pierre Plocco, Jérôme Guinard, Elisa Demonchy, Eric Cua, Edouard Devaud, Stanislas Harent, Marion Parisey, Céleste Lambert, Elise Gobin, Julien Manson, Pierre Pasquier, Pascale Martres, Patricia Kessedjian, Hikombo Hitoto, Nicolas Crochette, Lucia Perez-Grandiere, Jean-Baptiste Laine, Arnaud Salmon-Rousseau, Guillaume Cosseron, Sophie Blanchi, Florence Ader, Valérie Galvan, Alexia Moulin, Corinne Brochier, Julianne Oddone, Maude Bouscambert-Duchamp, Firouzé Bani-Sadr, Yohan N'guyen, Maxime Hentzien, Cédric Castex, Philippe Benoit, Véronique Brodard, Didier Laureillard, Albert Sotto, Paul Loubet, Aurélie Martin, Régine Doncesco, Julien Mazet, Ian Soulairol, Robin Stephan, François Goehringer, Nathalie Thilly, Michel Prevot, Hélène Jeulin, Jean-Philippe Talarmin, Lydie Khatchatourian, Nadia Saidan, Brice Guerpillon, Pascaline Rameau, Nicolas Cassou, Thomas Briand, Florence Le Gall, Elodie Le Breton, Cédric Joseph, Sandrine Soriot-Thomas, Claire Andrejak, Jean-Philippe Lanoix, Sophie Boddaert, Sandrine Castelain, Vincent Pestre, Juliette Woessner, Sophie Bayle, Stéphanie Branger, Christine Christides, Philippe Bielefeld, Adèle Lacroix, Roselyne Pillard-Gagliano, Isabelle Trinh, Pierre Lafitte, Guillermo Giordano, Malena Finello, Ignacio Ledesma, Gustavo Martini, Benjamin Delafontaine, Iris Corus, Pierre Baby, Emilie Catherinot, Céline Goyard, Simon Chauveau, Jad Choucair, Beatrice D'urso, Marie Da Silva Costa, Lucie Le Meur, Marc Vasse, Tiffany Pascreau, Eric Farfour, Benjamin Dervieux, C Charlotte Kaeuffer, François Danion, Yves Hansmann, Nicolas Lefebvre, Yvon Ruch, Axel Ursenbach, Catherine Schmidt-Mutter, Muhtadi Suliman, Anne Hutt, Guillaume Becker, Elodie Laugel, Sophie Bayer, Vincent Dubee, Rafael Mahieu, Valérie Daniel, Caroline Lefeuvre, Alexandra Ducancelle, Jean-Charles Gagnard, Abolfzl Mohebbi, Mélanie Dehais, Sophie Raccah, Anne-Lise Pouliquen, Alison Klasen, Emmanuel Forestier, Marie-Christine Carret, Severine Liardot, Jérôme Grosjean, Jean-François Faucher, Josselin Brisset, Anne Cypierre, Hélène Durox, Pauline Pinet, Sophie Ducroix-Roubertou, Claire Genet, Christine Vallejo, Sébastien Hantz, Marie Gousseff, Antoine Merlet, Sébastien Bigot, Marion Girard De Courtilles, Pascal Pouedras, Delphine Lariviere, Renaud Verdon, Sylvie Dargere, Jocelyn Michon, Anna Fournier, Sylvie Brucato, Séverine Gautier, Cécile Valentin, Anne Ricci, Antoine Alix, Flore Lacassin-Beller, Sophie Rousseau, Jérôme Dimet, Anne-Hélène Boivin, Maylis Larregle, Guillaume Rousseau, Ady Assaf, Fanny Vuotto, Karine Faure, Camille Joachim, Laurence Bocket, Kévin Diallo, Jessy Saffore, Isabelle Madeline, Pauline Chabanon, Nathalie Allou, Elisabeth Fernandes, Anne-Sophie Gruliere, Elisabeth Botelho-Nevers, Amandine Gagneux-Brunon, Véronique Ronat, Nadine Casimir, Sylvie Pillet, Frédérique Bertholon, Gilles Pialloux, Marwa Bachir Elrufaai, Ruxandra Calin, Pélagie Thibaut, Fatima Tendjaoui, Julie Fillon, Laurence Morand-Joubert, Marc-Olivier Vareil, Heidi Wille, Philippe Menager, Hugues Cordel, Youssouf Mohammed-Kassim, Vanessa Rathouin, Ségolène Brichler, André Cabie, Mélanie Lehoux, Karine Guitteaud, Karamba Sylla, Bastien Bigeard, Valentine Campana, Isabelle Calmont, Jean-Louis Lamaignere, Marine Deppenweiller, Christophe Padoin, Marine Thilbault, Laurence Fagour, Fatiha Najioullah, Isabelle Komla-Soukha, Mariam Roncato-Saberan, Martin Martinot, Mahsa Mohseni Zadeh, Simon Gravier, Ciprian Ion, Damien Kayser, Anne Schieber Pachart, Magali Eyriey, Anaïs Henric, Jean Daniel Kaiser, Dominique De Briel, Odile Duvaux, Gwenaëlle Evanno, Pierre-Joseph Royer, Juliette Rousse, Carine Ciron, Elsa Lhériteau, Gaëtane Rouvray, Alan Mougeolle, Auriane Rillet, Sophie Despons, Edwige Mevel, Françoise Shneiker, Régis Josien, Cécile Braudeau, Sophie Brouard, Hoa le Mai, Elise Appau-Danquah, Amélie Daniel, Virginie Grybek, David Gueneau, Marion Gautier, Joëlle Martin-Gauthier, Emily Rebouilleau, Joseph Herault, Tanguy Roman, Sorady Plantard, Patrice Chauveau, Anne Chiffoleau, Stéphanie Thauvin, Laurent Flet, Martine Tching-Sin, Eugenie Clapeau, Isabelle Charreau, Bruno Hoen, Caroline Solas-Chesneau, Astrid Vabret

Affiliations

¹ Nantes Université, CHU Nantes, INSERM, Department of Infectious Diseases, Nantes, France.
² Nantes Université, CHU Nantes, INSERM, Center for Research in Transplantation and Translational Immunology, Nantes, France.
³ Xenothera, Nantes, France.
⁴ INSERM, AP-HP, Hôpital Saint-Antoine, Service des Maladies Infectieuses et Tropicales, Institut Pierre Louis d'Epidémiologie et de Santé Publique, Sorbonne Université, Paris, France.
⁵ Infectious Diseases and Emergency Department, Centre Hospitalier de La Roche sur Yon, La Roche sur Yon, France.
⁶ CHU d'Orléans, Department of Infectious Diseases, Orleans, France.
⁷ Nantes Université, CHU Nantes, Sponsor Department, Direction de la Recherche et de l'Innovation, Nantes, France.
⁸ Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire d'Angers, Angers, France.
⁹ Univ Angers, Nantes Université, INSERM, Immunology and New Concepts in ImmunoTherapy, INCIT, Angers, France.
¹⁰ Nantes Université, CHU Nantes, Virology Laboratory, Nantes, France.
¹¹ Nantes Université, CHU Nantes, Laboratoire d'Immunologie, CIMNA, Nantes, France.
¹² Nantes Université, CHU Nantes, Plateforme de Méthodologie et Biostatistique, Direction de la Recherche et de l'Innovation, Nantes, France.
¹³ Nantes Université, CHU Nantes, UMR 1246 MethodS in Patients-centered outcomes and HEalth Research," SPHERE, Nantes, France.
¹⁴ Nantes Université, CHU Nantes, Clinical Pharmacology Department, Nantes, France.
¹⁵ CNRS, UMR5308, Ecole Normale Supérieure de Lyon, Centre International de Recherche en Infectiologie (CIRI), Inserm 1111, Université Claude Bernard Lyon 1, Université Lyon, Lyon, France.
¹⁶ Département des Maladies Infectieuses et Tropicales, Hospices Civils de Lyon, Lyon, France.

Abstract

Background: We evaluated the safety and efficacy of XAV-19, an antispike glyco-humanized swine polyclonal neutralizing antibody in patients hospitalized with severe coronavirus disease 2019 (COVID-19).

Methods: This phase 2b clinical trial enrolled adult patients from 34 hospitals in France. Eligible patients had a confirmed diagnosis of severe acute respiratory syndrome coronavirus 2 within 14 days of onset of symptoms that required hospitalization for low-flow oxygen therapy (<6 L/min of oxygen). Patients were randomly assigned to receive a single intravenous infusion of 2 mg/kg of XAV-19 or placebo. The primary end point was the occurrence of death or severe respiratory failure between baseline and day 15.

Results: Between January 12, 2021, and April 16, 2021, 398 patients were enrolled in the study and randomly assigned to XAV-19 or placebo. The modified intention-to-treat population comprised 388 participants who received full perfusion of XAV-19 (199 patients) or placebo (189 patients). The mean (SD) age was 59.8 (12.4) years, 249 (64.2%) individuals were men, and the median time (interquartile range) from symptom onset to enrollment was 9 (7-10) days. There was no statistically significant decrease in the cumulative incidence of death or severe respiratory failure through day 15 in the XAV-19 group vs the placebo group (53/199 [26.6%] vs 48/189 [25.4%]; adjusted risk difference, 0.6%; 95% CI, -6% to 7%; hazard ratio, 1.03; 95% CI, 0.64-1.66; P = .90). In the safety population, adverse events were reported in 75.4% of 199 patients in the XAV-19 group and in 76.3% of 190 patients in the placebo group through D29.

Conclusions: Among patients hospitalized with COVID-19 requiring low-flow oxygen therapy, treatment with a single intravenous dose of XAV-19, compared with placebo, did not show a significant difference in terms of disease progression at day 15.

Keywords: SARS-CoV-2; XAV-19; clinical trial; polyclonal glyco-humanized anti-SARS-CoV-2 antibody.