| Autor: |
Natalie I. Mazur, Yvette N. Löwensteyn, Jonne Terstappen, Jeanette Leusen, Fred Schobben, Daniela Cianci, Peter M. van de Ven, Stefan Nierkens, Louis J. Bont, Elisabeth E. Nibbelke, Brigitte Buiteman, Neele Rave, Marlies Vermaas-van Putten, Elly A. Smit-Kleinlugtenbeld, Jacqueline P. de Lege-Korstanje, Marieke G. Peetsold, Anthon Hulsmann, Sandy van Gool, Yvonne Snepvangers, Max Colombijn, Negassi Menelik, Stephanie de Crom, Ben Semmekrot, Wouter J. de Waal, Eline Okhuijsen, Gavin W. ten Tusscher, Ronald A. de Moor, Mijke A. Breukels, Claire Lutterman, Gerdien A. Tramper-Stranders, Johanna H. Oudshoorn, Astrid Ritman, Jeannette S. von Lindern, Gerdina H. Dubbink-Verheij, Maartje M. van den Berg, Marlon E.F. Wilsterman, Edwin Rietveld, Willemijn van Heel, Anne M. de Grauw, Femke Croes, Rienus A. Doedens, Lonneke van Onzenoort-Bokken, Clemens B. Meijssen, Machteld van Scherpenzeel-de Vries, Petra Hoekstra, Linda G.M. van Rooij, Willem-Pieter de Boode, Maaike C. van Rossem, Petra Sipkema, Monique A.M. Jacobs, Marianne A. van Houten, Indrani Kok-Wijesinha, Arine M. Vlieger, Walter Balemans, Frans B. Plötz, Naomi Reijmerink, Stefan M. van Dorth, Willem Heikens, Anke G. Kuijpers, Christel Geesing, Bas J.P. Delsing, Mieke Aldenhoven, Karoly Illy, Eric Hack, Floris Groenendaal, Nicole Derksen, Katrien Oude Rengerink, Jan Meeldijk, Lysette Ebskamp-van Raaij, Jolanda D.F. de Groot-Mijnes, Rob Schuurman |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
EClinicalMedicine, Vol 66, Iss , Pp 102324- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-5370 |
| DOI: |
10.1016/j.eclinm.2023.102324 |
| Popis: |
Summary: Background: Mucosal administration of monoclonal antibodies (mAbs) against respiratory pathogens is a promising alternative for systemic administration because lower doses are required for protection. Clinical development of mucosal mAbs is a highly active field yet clinical proof-of-concept is lacking. Methods: In this investigator-initiated, double-blind, randomized placebo-controlled trial, we evaluated intranasal palivizumab for the prevention of RSV infection in preterm infants (Dutch Trial Register NTR7378 and NTR7403). We randomized infants 1:1 to receive intranasal palivizumab (1 mg/mL) or placebo once daily during the RSV season. Any RSV infection was the primary outcome and RSV hospitalization was the key secondary outcome. The primary outcome was analyzed with a mixed effect logistic regression on the modified intention-to-treat population. Findings: We recruited 268 infants between Jan 14, 2019 and Jan 28, 2021, after which the trial was stopped for futility following the planned interim analysis. Adverse events were similar in both groups (22/134 (16.4%) palivizumab arm versus 26/134 (19.4%) placebo arm). There were 6 dropouts and 168 infants were excluded from the efficacy analyses due to absent RSV circulation during the SARS-CoV-2 pandemic. Any RSV infection was similar in infants in both groups (18/47 (38.3%) palivizumab arm versus 11/47 (23.4%) placebo arm; aOR 2.2, 95% CI 0.7–6.5). Interpretation: Daily intranasal palivizumab did not prevent RSV infection in late preterm infants. Our findings have important implications for the clinical development of mucosal mAbs, namely the necessity of timely interim analyses and further research to understand mucosal antibody half-life. Funding: Funded by the Department of Pediatrics, University Medical Centre Utrecht, the Netherlands. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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