180-day efficacy of nirsevimab against hospitalisation for respiratory syncytial virus lower respiratory tract infections in infants (HARMONIE): a randomised, controlled, phase 3b trial

作者：Alasdair Peter Stuart Munro, Simon B. Drysdale, Katrina Cathie, Florence Flamein, Markus Knuf, Andrea M. Collins, Helen C. Hill, Friedrich Kaiser, Robert Cohen, Didier Pinquier, Natalya Vassilouthis, Mariana Carreno, Catherine A. Moreau, Pierre Bourron, Lydie Marcelon, Karine Mari, Michelle Roberts, Pierre Tissières, Simon Royal, Saul N. Faust, France, Jacques Brouard, Andre Leke, Veronique Brevaut-Malaty, Chloe Epiard, Florence Flamein, Ralph Epaud, David Somerville, Franck Thollot, Phu My Tran Dinh, Mathie Lorrot, Andreas Werner, Rachel Froget, Hasinirina Razafimahefa, Michael Fayon, Camille Brehin, Pascal Boileau, Kim-An Nguyen, Cecile Guiheneuf, Claire Lefevre, Claire Sarreau, Fabienne Kochert, Frederic Huet, Elisa Seror, Fabienne Cahn-Sellem, Nadege Delavie, Christophe Batard, François Corrard, Morched Zouari, Nathalie Gelbert-Baudino, Diane Carriere, Zoha Maakaroun-Vermesse, Jean Gaschignard, Stephane Rioualen, Frederic Dugelay, Alain Wollner, Kai Kassmann, Didier Pinquier, Jean-Francois Delobbe, Robert Cohen, Anne Cheve, Anne Bourlet, Christele Gras-Le Guen, Benedicte Nold, Bergengere Kireche, Anne-Sylvestre Michot-Cottias, Francine Lecaillier, Myrna Achkar, Lisa Giovannini-Chami, Aimen Bsila, Laura Vivalda, Florence Goehringer, Amelie Poidvin, Christine Magendie, Emilie Georget, Blandine Desse, Vincent Gajdos, Didier Pinquier, Eric Jeziorski, Sanaa Naji, Christian Petit, Mallorie Mondenx, Emmanuelle Rondeleux, Aurelie Morand, Cecile Kerdudo-Veau, Blandine Prevost, Alexandra David, Gaelle Cornen, Christine Devulder, Sven Wellmann, Cordula Koerner-Rettberg, Otto Laub, Hartmut Scheele, Manfred Praun, Markus Knuf, Martin Wetzke, Helmut Pabel, Andreas Petri, Ulrich Thome, Falko Panzer, Hans Fuchs, Jana-Katharina Dieks, Martin Oliver Bauer, Jost Richter, Katrin Biebach, Frank Radowsky, Matthias Donner, Katja Denneberg, Jurgen Funck, Soeren Westerholt, Michael Horn, Malte Cremer, Wolfgang Kamin, Ulf Schulze-Sturm, Nikolaos Konstantopoulos, Brigitte Wilmsmeyer, Thomas Voelkl, Martina von Poblotzki, Andreas Mueller, Egbert Leonhardt, Siegfried Simmet, Eivy Franke-Beckmann, Stefan Eber, Thorsten Froehlich, Matthias Gorenflo, Eckard Hamelmann, Tobias Borchers, Ralph Koellges, Frank Jochum, Florian Brinkert, Monika Gappa, Christiane Lex, Sonja Behrendt, Adriana Haus, Eva Hahn, Sebastian Wirth, Ralph Maier, Sebastian Horn, Gergely Sarkoezy, Katja Weiss, Lutz Hempel, Friedrich Ebinger, Franziska Schaaff, Tilman Humpl, Torsten Ott, Louisa van den Boom, Dominik Schneider, Stephan Gehring, Ludwig Stapenhorst, Donald Wurm, Stefan Debler, Viola Gerstmann, Ralph Melchior, Joel Iffland, Norbert Teig, Tina-Maria Weichert, Thomas Glatzel, Eva Galiza, Elizabeth Whittaker, Nick Wooding, Sunil Bhimsaria, Patrick Moore, Nick Thomas, Sanjay Salgia, Anu Goenka, Timothy Johnson, Mildred Iro, Shye-Wei Wong, Arshid Murad, Samuel Oddie, Kelechi Ugonna, Clare Murray, Balaji Suryanarayanan, Nicola Millen, Sian Ludman, Nafeesa Arshad, Aung Soe, John Jackson, Manu Vatish, Dominic Smith, Paul Clarke, Chidambara Harikumar, Nicola Lester, Srinivas Bandi, Simon Royal, Athanasios Konstantinidis, Daniel Hawcutt, Lawrence Barnes, Rebecca Mann, Carrie Heal, Dinakaran Jayachandran, Amardeep Heer, Dinakaran Jayachandran, Charusheela Bhatia, Paul Fleming, Julian Forton, Ahmet Fuat, Basheer Peer-Mohamed, Victoria Robinson, Marieke Emonts, Nicholas Jacobsen, Samuel Davies, Girish Gowda, Camelia Vaina, Katrina Cathie, Otilia Popescu, James Kennard, Haji Khan, John Chapman, Krishna Jada, Jose-Ramon Fernandez-Alvarez, Prakash Kamath, Ian Binnian, Sarah Rayne, Clara Thompson, Binu Anand, Clare Hollingsworth, Timothy Scorrer, Vennila Ponnusamy, Christina Oliver, Christopher Bedford, Nilanjana Ray, Seethwakage Seram, Carolyn Paul, Damien McNally, William Priestman, William White, Stuart Mackay-Thomas, Claire Chalmers-Watson, Nilesh Agrawal, Atul Gupta, John Ryan, Alan Cade, Matthew Gaw, Claire Hombersley, Jonathan Cohen, Sweta Jain, Thomas Morgan, Clare Webster, Tamsin Simpkins, Mo Roshan, David Lewis, Katharine McDevitt, Mark Tighe, Charles Deakin, Vimal Vasu, Bushra Abdul Malik, Michael Yanney, James Perry, Ruth Cowie, Helen Purves, Bindu Radha, Lucinda Winckworth, Mark Danielsen, Rosaline Garr, Sanjay Rawal, Pete Wilson, Zelda Cheng, Adejumoke Awoseyila, Sebastian Gray, Lucy Martin, Laurence Cribbin, Rebecca Brown, Richa Gupta, Kevin Pender, Graham Roberts, Richard Burkimsher · 发表于：The Lancet Child & Adolescent Health · 年份：2025 · DOI：10.1016/s2352-4642(25)00102-6 · 被引用次数：53 · 研究领域：Respiratory viral infections research、Virus-based gene therapy research、COVID-19 Clinical Research Studies

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infection and hospitalisations in infants worldwide. The primary analyses of HARMONIE showed that nirsevimab reduced infant hospitalisations due to RSV-associated lower respiratory tract infection through the RSV season. This analysis aims to evaluate nirsevimab's efficacy at 180 days after dosing, a period exceeding the typical 5-month RSV season. METHODS: HARMONIE is an ongoing, open-label, parallel arm, randomised, controlled, phase 3b study conducted in France, Germany, and the UK. Infants aged 12 months or younger, born at a gestational age of at least 29 weeks, were randomly assigned (1:1) to receive either a single intramuscular dose of nirsevimab (50 mg for children <5 kg or 100 mg for children ≥5 kg) or standard care (without RSV prophylaxis) before or during their first RSV season. Randomisation was electronically done, stratified by country and age-group. The primary efficacy endpoint for this analysis was the incidence of hospitalisations due to RSV-associated lower respiratory tract infection up to 180 days after nirsevimab administration or randomisation in all randomised participants. Safety up to 365 days following nirsevimab administration was also assessed. This trial is ongoing and registered with ClinicalTrials.gov, number NCT05437510. FINDINGS: Between Aug 8, 2022, and Feb 28, 2023, 8057 infants were randomly assigned to either the nirsevimab group (n=4038) or the ...