1. Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trialResearch in context
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Andrea Alemany, Pere Millat-Martinez, Marc Corbacho-Monné, Clara Suñer, Cristina Galvan-Casas, Caty Carrera, Dan Ouchi, Núria Prat, Jordi Ara, Nuria Nadal, Ricard Riel, Blanca Funollet, Carmen Ojeda-Ciurana, Lluis Esteve Balague, Betlem Salvador-González, Anna Forcada Arcarons, Josep Vidal-Alaball, María Isabel Del Cura-González, Ricardo Rodríguez Barrientos, Rafel Ramos-Blanes, Alberto Alum Bou, Elsa Mondou, Mireia Torres, Neus Campins, Ana Sanz, Yonggiang Tang, Miquel Àngel Rodriguez-Arias, Quique Bassat, Bonaventura Clotet, Oriol Mitjà, Adrià Aguilar-Uroz, Adrià Rosell-García-Ufano, Adrián Escudero Planas, Aida Baelo, Ainhoa Villahoz Martín, Alberto Moreno López, Alberto Roldan Ruiz, Alberto Santana Briongos, Alberto Tejera Bodas, Alejandro Alonso-Vallés, Alejandro Fletes-Pérez, Alejandro Hueso-Mor, Alex Boluda, Alex Santamaria, Alicia Santos Diestro, Almudena Revuelta-Álvarez, Álvaro Moreno Moreno, Ana Ortega de Felipe, Ana Chen-Ye, Ana Blázquez Valerón, Ana Belén Rodríguez Pérez, Ana Laura Tristán Morgalo, Ana Luisa Fernández-Allende, Andrea Bagán-Trejo, Andrés Fernández Juan, Ángel Zalve-Cano, Anna Mateo-Martínez, Antonio Valero Galván, Antonio Egidos-Plaja, Ariadna Jorge, Arturo Fraile Torres, Azahara Maria Pareja Leal, Bárbara Viader Castro, Barbara Fernandez Beato, Barbara Naveira Menchen, Beatriz Martin Poyatos, Beatriz García-Martínez, Belén Rodrigo Testillano, Belen Blanco Tejedor, Blanca López Pérez, Blanca Mencía Hernanz, Camila González-Beiras, Carlos Batres, Carmen Nuñez Garcia, Carmen Merino-Rodríguez, Carolina Rodríguez-Gilabert, Celia Bonilla Penedo, Christian Casado Gomez, Claudia Gonzalez Perez, Claudia Galindo-Tomás, Cristina Peral Bolaños, Cristina Blanco-Montes, Cristina Lupu-Yakovleva, Cristina Lopez Ruiz, Cristina Perez Mayoral, Cristina Fornes, Cristobal Garcia Corrochano, Daniel Gallardo Álvarez, Daniel Navarro Sanz, David Sanz Barrio, Debora Ramet Meseguer, Edna Margarita Vera-Jurado, Eduardo Perez Costa, Eilen Junet Bustillos-Sebastian, Elena Palomar Casado, Elena Dorrego Guerrero, Elena Medina Mateos, Elisa Rebeca Aragón Gaspar, Elisabeth Herrero-Vila, Enriqueta Paez Herrera, Esmeralda Rojas Powel, Esther Robres Medialdea, Esther Vall-Ribalta, Eva Lopez Perez, Felicia Mihaela Fer, Fernanda Vazquez Ángeles, Fernando Tirado Bejarano, Ferran Prats-Domenech, Ferran Borràs Martí, Gabriela Ardila-Mejia, Gèlia Costes, Gema Gómez Arquero, Gemma Flores Mateo, Guillem Pintos-Morell, Helena Mira-Centelles, Ignacio Astola Requena, Ignacio Ortega Martin, Iker Leivas-Gutierrez, Irene Escribano Valenciano, Irene Muñoz Gomez, Irina Ortega, Isabel Montserrat-Lloan, Itziar Gamboa, Jacobo Rodríguez de Torres de Paul, Jordi Cahís, Jordi Muñoz-Martinez, Jorge Iglesias Bermejo, Joselvis Virginia Cejas López, Josep Canudas, Juan Antonio García Lucas, Juan Carlos Martínez-Pino, Juana Torres Martínez, Judit Pujol-Corney, Judith González Jiménez, Júlia Gurí, Julio Labella Martín, Laia Garcia-Cano, Lara Sonsoles Perez Plata, Laura Muñoz Álvaro, Laura Rodríguez Andrés, Laura Vega Ruiz, Laura Cuevas Valiente, Laura Díaz Rodríguez, Laura Puigros, Lavinia Oristina Rciorang, Leticia Escudero, Liliana Figueroa Caballero, Lluna Ferrerfàbrega-Costals, Lucía Costafreda-Hernández, Lucía De-Paúl, Luis González Fernández-Medina, Ma Carmen Moliner Prada, Ma Cristina Berriochoa Martínez de Pisón, Maria Blanco Blasco, Maria Gil Jorge, María Cortijo Caballero, Maria Ubals, Maria Gordillo, Maria Alicia Guilloto López, Maria Concepción Moreno Calvo, María del Rosario Gil García, María Inmaculada Dueñas Román, Maria Josefa Gonzalez Sanchez, María Luisa Nicolás Campoy, Maria Luz González Velayos, Mario Mejías Zori, Mario Oliva Maqueda, Mario Caño de la Cruz, Mariona Palau-Morral, Marta Martín-Muñoz, Marta Cereceda Meca, Marta Díaz Urbina, Martha VerónicaPlazas, Martí Vall-Mayans, Martí Blasco, Mary Jane Chu-Sifuentes, Miguel García de Villasladad Peñaranda, Miguel Hernanz Sotoca, Miguel Iglesias Gonzalez, Miguel Ángel Labrador-Galván, Miguel Rodrigo de Vivar Azcarate, Miquel Gil-Fibla, Miquel Formentí-Pallarés, Mireia Esteve-Tugues, Miriam Juanes Perez, Miriam López Rubio, Mirian Recuero Renales, Mònica Hijós-Rullo, Montserrat Lleonart-Abadia, Nadia Finelli, Naiara Rojas-Bertier, Nataly Reyes-Calderón, Nerea Casado Larrañaga, Nerea Nuria Zurita Castrosin, Noélia Álvarez-Nieto, Nuria Leiva-Mora, Olga Tomillo-Martín, Omar Belghazi, Oriol Buscà, Pablo Mendoza Cediel, Pablo Macedo, Patricia Rodríguez Barroso, Patricia Ruiz Álvarez, Patricia Morales López, Patricia Jimenez Vara de Rey, Paz Lozano Ginés, Pilar Bris Rodriguez, Pilar Martínez-Alamillo, Rafa Salmerón Martínez, Raquel Botello Ariza, Raquel Vaquero Mena, Raquel González-Alonso, Raul Kaczmarczyk, Rita Barnadas Vintró, Rodrigo Hontecillas Martínez, Rosa Ribot-Rodríguez, Rosa Escobar-Sánchez, Rosario Paloma Montes Trinidad, Rubén Martínez Quintana, Ruben Arnay Arrogante, Ruben Berjon Sanchez, Ruben Picazo Navarro, Rubén Bastos, Samuel Martín Molinero, Samuel Dan Israel-Benchaya, Sandra Muñoz-Burguillo, Sandra Rodríguez-Salvador, Sara Avila, Sara Corral Gayubas, Sergio Nuñez Sánchez, Sofía Torres Weber, Susana Encabo Lopez, Teresa Torices Rasines, Valentí Sallas, Verónica Curto-Vicente, Verónica Gómez Hijosa, Verónica Daimiel-Pedrote, Verónica Gozalo, Vicente Barrios López, Virginia Ivette Castillo Montoya, Yuri Espinoza Pérez, María CristinaBerriochoa Martínez de Pisón, David Muñoz Castillo, Carlos Donato, and Isabel García García
- Subjects
Hyperimmune immunoglobulin ,Antibody therapies ,COVID-19 ,SARS-CoV-2 ,Outpatients ,Asymptomatic individuals ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, −3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; −9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.
- Published
- 2023
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