2026-04-17T03:49:11Zhttps://recercat.cat/oai/requestoai:recercat.cat:11351/138762025-10-24T10:39:03Zcom_2072_378070com_2072_378040col_2072_378092
RECERCAT
author
Mall, Marcus
author
Wainwright, Claire
author
Legg, Julian
author
Chilvers, Mark
author
Dittrich, Anna-Maria
author
Gartner, Silvia
2025-10-24T10:39:03Z
2025-10-24T10:39:03Z
2025-10-16T07:26:38Z2025-10-16T07:26:38Z2025
http://hdl.handle.net/11351/13876
Children; Cystic fibrosis; MutationNens; Fibrosi quística; MutacióNiños; Fibrosis quística; MutaciónBackground: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in children aged 6-11 years with cystic fibrosis (CF) heterozygous for F508del and a minimal function CF transmembrane conductance regulator (CFTR) variant (F/MF genotypes) in a 24-week, placebo-controlled trial. We conducted a 96-week open-label extension study for children who completed the 24-week parent study.
Methods: In this phase 3b extension study, dosing was based on weight and age, with children weighing <30 kg and aged <12 years receiving ELX 100 mg once daily, TEZ 50 mg once daily and IVA 75 mg every 12 h, and children ≥30 kg or ≥12 years receiving ELX 200 mg once daily, TEZ 100 mg once daily and IVA 150 mg every 12 h. The primary end-point was safety and tolerability. Secondary and other efficacy end-points included absolute changes from parent study baseline in sweat chloride concentration, lung clearance index (LCI2.5), percentage predicted forced expiratory volume in 1 s (FEV1) and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.
Results: A total of 120 children were enrolled and dosed. 118 children (98.3%) had adverse events (AEs), which for most were mild (43.3%) or moderate (48.3%) in severity. The most common AEs (≥20% of children) were COVID-19 (58.3%), cough (51.7%), nasopharyngitis (45.0%), pyrexia (40.0%), headache (37.5%), upper respiratory tract infection (30.8%), oropharyngeal pain (26.7%), rhinitis (24.2%), abdominal pain (22.5%) and vomiting (20.0%). Children who transitioned from the placebo and ELX/TEZ/IVA groups of the parent study had improvements from parent study baseline at Week 96 in mean sweat chloride concentration (-57.3 (95% CI -61.6- -52.9) and -57.5 (95% CI -62.0- -53.0) mmol·L-1), LCI2.5 (-1.74 (95% CI -2.09- -1.38) and -2.35 (95% CI -2.72- -1.97) units), FEV1 % pred (6.1 (95% CI 2.6-9.7) and 6.9 (95% CI 3.2-10.5) percentage points) and CFQ-R respiratory domain score (6.6 (95% CI 2.5-10.8) and 2.6 (95% CI -1.6-6.8) points).
Conclusions: ELX/TEZ/IVA treatment was generally safe and well tolerated, with a safety profile consistent with the parent study and older age groups. After starting ELX/TEZ/IVA, children had robust improvements in sweat chloride concentration and lung function that were maintained through 96 weeks. These results demonstrate the safety and durable efficacy of ELX/TEZ/IVA in this paediatric population.This study was funded by Vertex Pharmaceuticals Incorporated. Supported by the National Institute of Health and Care Research through the Imperial Biomedical Research Centre, the Brompton Clinical Research Facility and a Senior Investigator Award (to J.C. Davies).
Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess
Avaluació de resultats (Assistència sanitària)
Anomalies cromosòmiques
Fibrosi quística - Tractament
Pulmons - Malalties
ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Diagnosis::Prognosis::Treatment Outcome
PHENOMENA AND PROCESSES::Genetic Phenomena::Genetic Variation::Mutation
DISEASES::Digestive System Diseases::Pancreatic Diseases::Cystic Fibrosis
DISEASES::Respiratory Tract Diseases::Lung Diseases::Cystic Fibrosis
CHEMICALS AND DRUGS::Pharmaceutical Preparations::Drug Combinations
TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::diagnóstico::pronóstico::resultado del tratamiento
FENÓMENOS Y PROCESOS::fenómenos genéticos::variación genética::mutación
ENFERMEDADES::enfermedades del sistema digestivo::enfermedades pancreáticas::fibrosis quística
ENFERMEDADES::enfermedades respiratorias::enfermedades pulmonares::fibrosis quística
COMPUESTOS QUÍMICOS Y DROGAS::preparados farmacéuticos::combinaciones de fármacos
Elexacaftor/tezacaftor/ivacaftor in children aged ≥6 years with cystic fibrosis heterozygous for F508del and a minimal function mutation: results from a 96-week open-label extension study
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion