Safety and Efficacy of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies Amubarvimab Plus Romlusevimab in Nonhospitalized Patients With COVID-19

作者：Teresa H. Evering, Kara W. Chew, Mark J Giganti, Carlee Moser, Mauricio Pinilla, David Alain Wohl, Judith S. Currier, Joseph J. Eron, Arzhang Cyrus Javan, Rachel Bender Ignacio, David M. Margolis, Qing Zhu, Ji Ma, Lijie Zhong, Yan Li, Ulises D’Andrea Nores, Keila Hoover, Bharat Mocherla, Manish C. Choudhary, Rinki Deo, Justin Ritz, William A. Fischer, Courtney V. Fletcher, Jonathan Z. Li, Michael D. Hughes, Davey M. Smith, Eric S. Daar, ACTIV-2/A5401 Study Team, Teresa H. Evering, Kara W. Chew, Mark J Giganti, Carlee Moser, David Alain Wohl, Judith S. Currier, Joseph J. Eron, Arzhang Cyrus Javan, Rachel Bender Ignacio, David M. Margolis, Ulises D’Andrea Nores, Keila Hoover, Bharat Mocherla, Manish C. Choudhary, Justin Ritz, William A. Fischer, Courtney V. Fletcher, Jonathan Z. Li, Michael D. Hughes, Davey M. Smith, Eric S. Daar, Lara Hosey, Jhoanna Roa, Nilam Patel, Kelly Colsh, Irene Rwakazina, Justine Beck, Scott F. Sieg, Sandra Wagner Cardoso, Katya Corado, Prasanna Jagannathan, Nikolaus Jilg, Alan S. Perelson, Sandy Pillay, Cynthia Riviere, Upinder Singh, Babafemi Taiwo, Joan Gottesman, Matthew Newell, Susan Pedersen, Joan Dragavon, Cheryl Jennings, Brian Greenfelder, William Murtaugh, Jan Kosmyna, Morgan Gapara, Akbar Shahkolahi, Verónica Lacal, D. Salusso, Sebastián A Núñez, Marcelo Rodrigo Rodriguez, Luciana Laborde, Marcelo Papasidero, Luis Wehbe, Mariana González, F. Fernandez Voena, T. Alvarez, Amaru Lopez, V Huhn, Pablo Dieser, Fernando Bordese, Marisa Mussi, Rodrigo de Carvalho Santana, Adriana Aparecida Tiraboschi Bárbaro, Breno Santos, Rita de Cássia Alves Lira, Andre Luiz Machado da Silva, Maria Pia Diniz Ribeiro, Nathália Soliva, Eduardo Vasconcellos, Jorge Eurico Ribeiro, Miriam Amaral Enéas, Jorge Pinto, Júlia Fonseca de Morais Caporali, Flávia Gomes Faleiro Ferreira, Norma E. Rivera-Martínez, Víctor Casildo Bohórquez López, Melchor Victor Frias, Krystle Bliss Fetalvero, Alyxzza Maranan, Jennifer Rosa, Thomas Frederic Coetzer, Sr Maureen Mohata, Umesh Lalloo, Penelope Madlala, Larisha Pillay-Ramaya, Jaclyn Bennet, Noluthando Mwelase, Nokuphiwa Mbhele, Frederick Petrick, Leonard Joubert, Sr Rose Mbali, Natasha Joseph, Mmatsie Manentsa, Eugene van der Walt, Mduduzi Masilela, Zinhle Zwane, Tendai Chiperera, Lerato Mohapi, Suri Moonsamy, Usha Singh, Kirsten McHarry, Elizma Snyman, Pieter Lennox, James Craig Innes, Oteng Letlape, Olebogeng Jonkane, William Brumskine, Tania Adonis, Ni Ni Sein, Modulakgotla Sebe, Yacoob Vahed, Nazreen Jeewa Hussen, Ismail Mitha, Vasundhara Cheekati, Purna Cheekati, Christie Lummus, Samuel H Idarraga, Andrew Kim, David Pham, Wei-Hsin Kao, Michael M. Pfeffer, Miriam Batule Dominguez, Francisco Patron, Luz Guzman, E Juncadella Ferrer, Anju Malik, Anna Bryan, Melanie Arnold, Idania Fernandez, Cinzia Karpf, A. Bazzoni Ruiz, David Taylor, Eric Folkens, Jennifer Manne‐Goehler, Sigal Yawetz, Cheryl Keenan, Emeka Eziri, Carl J. Fichtenbaum, Jenifer Baer, Sarah Trentman, Robert S. Call, Leroy Vaughan, Aaron P. Milstone, Jamie Alex Slandzicki, Jessica Wallan, Clinton Guillory, Nancy Andrews, L E Hughes, Jonathan Berardi, Celine Arar, Randall Quinn, Jorge P. Amaya, Marissa Gomez-Martinez, Luis Cantu, Monica M. Betancourt-Garcia, Nwora Lance Okeke, Charles M. Burns, Fadi Haddad, Victoria Haddad, Jeanne-Elyse Cedeno, Lisbel Gonzalez, L. Pestana, Augusto Focil, Griselda Rosas, Susana Moyano, Yaneicy Gonzalez Rojas, Ahmad Aswad, Yevgeniy Bukhman, Manish Kumar Jain, Eugene Bukhman, Humam Farah, R. Michael McClain, Sadia Shaik, Timothy Hatlen, Deepa Gotur, Joseph Surber, Jeffrey S. Kingsley, April Pixler, Alex Zopo, Jack Herman, Craig Herman, Ramón Fernández de León, Boris Nikolov, Laurie Welton, Barbara Bromberg, Kelly Christina, Fernando Gonzalez Vergara, Ana Isabel González, Noemí González, Michael A. Gelman, Olga Andriunas, Zarema Jagizarov, Jan Westerman, David O. Davis, Donna Sherer, Kelly E. Dooley, Becky Becker, Adaliah Wilkins, J. Pérez, Eloy Roman, Heriberto Fernández, Kelly von Beck, V. Calatayud Maldonado, Jennifer Veltman, Rajesh T. Gandhi, Katrina Shea, M. Gustave Planchon, Laura Herpel, Kaushlendra K. Tripathi, Donald C. Day, John Pullman, Erin Williams-Leber, Misty Johnson, Michelle T. Hecker, Ann Avery, George W. Monlux, Elizabeth Juneja, Arthur Wernick, Karelia Ruiz, Maureen Hernández, Y. E. Ramírez Pérez, Claudia Hawkins, Baiba Berzins, Carlos Malvestutto, Heather Harber, Robyn Cicarella, Edwin DeJesus, Charlotte-Paige Rolle, Almena Free, Sallie D. Pulliam, D. Weinstein, Rosa Suárez, Ezequiel Socorro, Estefania Socorro, Gene Neytman, Jack Herman, Craig Herman, R. Blaine Easley, Mariam Aziz, J. A. Swiatek, Avish Nagpal, Breanna Kompelien, K McEvoy, Susan E. Hoover, A Lutz, Jessica Just, Manuel Hernandez, Yanly B. Victoria, Gabriel Rodríguez, Divya Pathak, Joshua J. Ordway, Megan Heffner, Patrick Weston, Khalilah Weston, Madhu Choudhary, Jennifer Sullivano, Olayemi Osiyemi, Myriam Izquierdo, Odelsey Torna, Brian M. Clemency, Renoj Varughese, Joshua Lynch, Aleen Khodabakhshian, Samantha Fortier, Christopher J. Coyne, Alexandrea Cronin, Constance A. Benson, Steven Hendrickx, Rosemarie Ramirez, Anne F. Luetkemeyer, Suzanne Hendler, Dennis Dentoni-Lasofsky, Mobeen H. Rathore, Saniyyah Mahmoudi, Amna Riaz, Mario Castro, Leslie Spikes, Chase Hall, Jonathan Oakes, Amy James Loftis, Pablo Tebas, William R. Short, Michael P. Dubé, Saahir Khan, Luis M. Mendez, Sarah McGuffin, Chris Jonsson, Mamta K. Jain, Smruthi Senthil, Kimberly Turner-Gray, Sanjay Mehta, Mary Lewinski, Masoud Azizad, Christopher Chow, Lisa Nakatani, Derrick Williamson, Hisham Atriss, Matthew Caloura, Midhun Malla, Hannah Hazard‐Jenkins, Aimee Wilkin, Jamraus Fayssoux, Hannah M. Seagle, Rachel M. Presti, Alem Haile · 发表于：Annals of Internal Medicine · 年份：2023 · DOI：10.7326/m22-3428 · 被引用次数：31 · 研究领域：SARS-CoV-2 and COVID-19 Research、COVID-19 Clinical Research Studies、vaccines and immunoinformatics approaches

Background:Development of safe and effective SARS-CoV-2 therapeutics is a high priority. Amubarvimab and romlusevimab are noncompeting anti–SARS-CoV-2 monoclonal antibodies with an extended half-life. Design:Randomized, placebo-controlled, phase 2 and 3 platform trial. (ClinicalTrials.gov: NCT04518410) Setting:Nonhospitalized patients with COVID-19 in the United States, Brazil, South Africa, Mexico, Argentina, and the Philippines. Patients:Adults within 10 days onset of symptomatic SARS-CoV-2 infection who are at high risk for clinical progression. Measurements:Nasopharyngeal and anterior nasal swabs for SARS-CoV-2, COVID-19 symptoms, safety, and progression to hospitalization or death. Results:Eight-hundred and seven participants who initiated the study intervention were included in the phase 3 analysis. Median age was 49 years (quartiles, 39 to 58); 51% were female, 18% were Black, and 50% were Hispanic or Latino. Median time from symptom onset at study entry was 6 days (quartiles, 4 to 7). Hospitalizations and/or death occurred in 9 (2.3%) participants in the amubarvimab plus romlusevimab group compared with 44 (10.7%) in the placebo group, with an estimated 79% reduction in events (P < 0.001). This reduction was similar between participants with 5 or less and more than 5 days of symptoms at study entry. Grade 3 or higher treatment-emergent adverse events through day 28 were seen less frequently among participants randomly assigned to amubarvimab plus romlusevimab (7.3%) t...