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 trial. (March 2023)

• Record Type: Journal Article
• Authors: Alemany, Andrea; Millat-Martinez, Pere; Corbacho-Monné, Marc; Suñer, Clara; Galvan-Casas, Cristina; Carrera, Caty; Ouchi, Dan; Prat, Núria; Ara, Jordi; Nadal, Nuria; Riel, Ricard; Funollet, Blanca; Ojeda-Ciurana, Carmen; Balague, Lluis Esteve; Salvador-González, Betlem; Arcarons, Anna Forcada; Vidal-Alaball, Josep; Del Cura-González, María Isabel; Barrientos, Ricardo Rodríguez; Ramos-Blanes, Rafel; Bou, Alberto Alum; Mondou, Elsa; Torres, Mireia; Campins, Neus; Sanz, Ana; Tang, Yonggiang; Rodriguez-Arias, Miquel Àngel; Bassat, Quique; Clotet, Bonaventura; Mitjà, Oriol; Aguilar-Uroz, Adrià; Rosell-García-Ufano, Adrià; Escudero Planas, Adrián; Baelo, Aida; Villahoz Martín, Ainhoa; Moreno López, Alberto; Roldan Ruiz, Alberto; Santana Briongos, Alberto; Tejera Bodas, Alberto; Alonso-Vallés, Alejandro; Fletes-Pérez, Alejandro; Hueso-Mor, Alejandro; Boluda, Alex; Santamaria, Alex; Diestro, Alicia Santos; Revuelta-Álvarez, Almudena; Moreno Moreno, Álvaro; Ortega de Felipe, Ana; Chen-Ye, Ana; Blázquez Valerón, Ana; Rodríguez Pérez, Ana Belén; Tristán Morgalo, Ana Laura; Fernández-Allende, Ana Luisa; Bagán-Trejo, Andrea; Fernández Juan, Andrés; Zalve-Cano, Ángel; Mateo-Martínez, Anna; Galván, Antonio Valero; Egidos-Plaja, Antonio; Jorge, Ariadna; Fraile Torres, Arturo; Pareja Leal, Azahara Maria; Viader Castro, Bárbara; Fernandez Beato, Barbara; Naveira Menchen, Barbara; Martin Poyatos, Beatriz; García-Martínez, Beatriz; Rodrigo Testillano, Belén; Blanco Tejedor, Belen; López Pérez, Blanca; Mencía Hernanz, Blanca; González-Beiras, Camila; Batres, Carlos; Batres, Carlos; Nuñez Garcia, Carmen; Merino-Rodríguez, Carmen; Rodríguez-Gilabert, Carolina; Bonilla Penedo, Celia; Bonilla Penedo, Celia; Casado Gomez, Christian; Gonzalez Perez, Claudia; Galindo-Tomás, Claudia; Peral Bolaños, Cristina; Blanco-Montes, Cristina; Lupu-Yakovleva, Cristina; Lopez Ruiz, Cristina; Perez Mayoral, Cristina; Fornes, Cristina; Garcia Corrochano, Cristobal; Gallardo Álvarez, Daniel; Navarro Sanz, Daniel; Sanz Barrio, David; Ramet Meseguer, Debora; Vera-Jurado, Edna Margarita; Perez Costa, Eduardo; Bustillos-Sebastian, Eilen Junet; Palomar Casado, Elena; Guerrero, Elena Dorrego; Medina Mateos, Elena; Aragón Gaspar, Elisa Rebeca; Herrero-Vila, Elisabeth; Paez Herrera, Enriqueta; Rojas Powel, Esmeralda; Robres Medialdea, Esther; Vall-Ribalta, Esther; Lopez Perez, Eva; Mihaela Fer, Felicia; Vazquez Ángeles, Fernanda; Tirado Bejarano, Fernando; Prats-Domenech, Ferran; Borràs Martí, Ferran; Ardila-Mejia, Gabriela; Costes, Gèlia; Gómez Arquero, Gema; Flores Mateo, Gemma; Pintos-Morell, Guillem; Mira-Centelles, Helena; Astola Requena, Ignacio; Ortega Martin, Ignacio; Leivas-Gutierrez, Iker; Escribano Valenciano, Irene; Muñoz Gomez, Irene; Ortega, Irina; Montserrat-Lloan, Isabel; Gamboa, Itziar; Rodríguez de Torres de Paul, Jacobo; Cahís, Jordi; Muñoz-Martinez, Jordi; Bermejo, Jorge Iglesias; Cejas López, Joselvis Virginia; Canudas, Josep; García Lucas, Juan Antonio; Martínez-Pino, Juan Carlos; Torres Martínez, Juana; Pujol-Corney, Judit; González Jiménez, Judith; Gurí, Júlia; Labella Martín, Julio; Garcia-Cano, Laia; Perez Plata, Lara Sonsoles; Muñoz Álvaro, Laura; Rodríguez Andrés, Laura; Vega Ruiz, Laura; Cuevas Valiente, Laura; Díaz Rodríguez, Laura; Puigros, Laura; Oristina Rciorang, Lavinia; Escudero, Leticia; Figueroa Caballero, Liliana; Ferrerfàbrega-Costals, Lluna; Costafreda-Hernández, Lucía; De-Paúl, Lucía; González Fernández-Medina, Luis; Moliner Prada, M Carmen; Berriochoa Martínez de Pisón, M Cristina; Blanco Blasco, Maria; Gil Jorge, Maria; Cortijo Caballero, María; Ubals, Maria; Gordillo, Maria; Guilloto López, Maria Alicia; Moreno Calvo, Maria Concepción; Gil García, María del Rosario; Dueñas Román, María Inmaculada; Gonzalez Sanchez, Maria Josefa; Nicolás Campoy, María Luisa; González Velayos, Maria Luz; Zori, Mario Mejías; Maqueda, Mario Oliva; Caño de la Cruz, Mario; Palau-Morral, Mariona; Martín-Muñoz, Marta; Cereceda Meca, Marta; Díaz Urbina, Marta; VerónicaPlazas, Martha; Vall-Mayans, Martí; Blasco, Martí; Jane Chu-Sifuentes, Mary; García de Villasladad Peñaranda, Miguel; Hernanz Sotoca, Miguel; Iglesias Gonzalez, Miguel; Labrador-Galván, Miguel Ángel; Rodrigo de Vivar Azcarate, Miguel; Gil-Fibla, Miquel; Formentí-Pallarés, Miquel; Esteve-Tugues, Mireia; Juanes Perez, Miriam; López Rubio, Miriam; Recuero Renales, Mirian; Hijós-Rullo, Mònica; Lleonart-Abadia, Montserrat; Finelli, Nadia; Rojas-Bertier, Naiara; Reyes-Calderón, Nataly; Casado Larrañaga, Nerea; Zurita Castrosin, Nerea Nuria; Álvarez-Nieto, Noélia; Leiva-Mora, Nuria; Tomillo-Martín, Olga; Belghazi, Omar; Buscà, Oriol; Mendoza Cediel, Pablo; Macedo, Pablo; Rodríguez Barroso, Patricia; Ruiz Álvarez, Patricia; López, Patricia Morales; Vara de Rey, Patricia Jimenez; Ginés, Paz Lozano; Bris Rodriguez, Pilar; Martínez-Alamillo, Pilar; Salmerón Martínez, Rafa; Botello Ariza, Raquel; Vaquero Mena, Raquel; González-Alonso, Raquel; Kaczmarczyk, Raul; Barnadas Vintró, Rita; Hontecillas Martínez, Rodrigo; Ribot-Rodríguez, Rosa; Escobar-Sánchez, Rosa; Montes Trinidad, Rosario Paloma; Martínez Quintana, Rubén; Arnay Arrogante, Ruben; Berjon Sanchez, Ruben; Picazo Navarro, Ruben; Bastos, Rubén; Martín Molinero, Samuel; Israel-Benchaya, Samuel Dan; Muñoz-Burguillo, Sandra; Rodríguez-Salvador, Sandra; Avila, Sara; Corral Gayubas, Sara; Nuñez Sánchez, Sergio; Torres Weber, Sofía; Encabo Lopez, Susana; Torices Rasines, Teresa; Sallas, Valentí; Curto-Vicente, Verónica; Gómez Hijosa, Verónica; Daimiel-Pedrote, Verónica; Gozalo, Verónica; Barrios López, Vicente; Castillo Montoya, Virginia Ivette; Espinoza Pérez, Yuri; CristinaBerriochoa Martínez de Pisón, María; Muñoz Castillo, David; Donato, Carlos; García García, Isabel;
• Is Part Of: EClinicalMedicine. Volume 57(2023)
• Publication Date: 2023-03
• Subjects: Hyperimmune immunoglobulin -- Antibody therapies -- COVID-19 -- SARS-CoV-2 -- Outpatients -- Asymptomatic individuals; Medicine -- Research -- Periodicals; Medical policy -- Periodicals; Clinical Medicine; Health Policy; Public Health; Medical policy; Medicine -- Research; Periodical; Electronic journals; Periodicals; 613
• DOI: 10.1016/j.eclinm.2023.101898
• Languages: English
• ISSNs: 2589-5370

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 .