Pulmonary endpoints in clinical trials for children with cystic fibrosis under two years of age
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Cystic fibrosis is a lifelong progressive disease in which lung disease is the main prognostic factor, where starting early treatment is crucial for improving long-term outcomes. Therefore, new treatment should be available as early as possible. However, choosing appropriate and feasible clinical trial endpoints in children under 2 years of age presents significant challenges. Most studies in this age group have extrapolated pulmonary efficacy from older age groups, focusing on safety, pharmacokinetics, and biomarker response. As lung health is near normal in infants, demonstrating absence of pulmonary decline requires large sample sizes and extended study duration, which may not be feasible for standard regulatory trials. To address this gap, the European Cystic Fibrosis Society Clinical Trials Network developed a consensus document evaluating direct pulmonary endpoints for therapeutic pulmonary studies in this young age group. The pulmonary endpoints evaluated include multiple-breath washout (MBW); chest computed tomography (CT); chest magnetic resonance imaging (MRI); airway infection and inflammation. Relevant literature, pitfalls, practice guidelines, and recommendations are presented. None of the pulmonary endpoints evaluated are currently suitable to serve as a primary efficacy endpoint in children below 2 years of age, as this will require large numbers and long follow-up. For clinical trials in infants with CF, pharmacokinetics, pharmacodynamics, safety and tolerability should remain the primary endpoints, with pulmonary endpoints as secondary or exploratory outcomes. Post authorization studies are essential to evaluate long-term pulmonary benefits, including MBW, structural lung assessment (e.g. CT and MRI), and markers of pulmonary inflammation to fully understand the impact of early therapy initiation in this young population.
Date Issued
2025-07-01
Date Acceptance
2025-06-23
Citation
Journal of Cystic Fibrosis, 2025, 24 (4), pp.669-683
ISSN
1569-1993
Publisher
Elsevier BV
Start Page
669
End Page
683
Journal / Book Title
Journal of Cystic Fibrosis
Volume
24
Issue
4
Copyright Statement
© 2025 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40615279
PII: S1569-1993(25)01517-6
Subjects
Chest CT
Chest MRI
Clinical trials
Infants
Infection
Inflammation
Multiple breath washout
Paediatrics
Pulmonary endpoints
Humans
Infant
Clinical Trials as Topic
Cystic Fibrosis
Endpoint Determination
Lung
Magnetic Resonance Imaging
Practice Guidelines as Topic
Tomography, X-Ray Computed
Infant, Newborn
Publication Status
Published
Coverage Spatial
Netherlands
Date Publish Online
2025-07-04