2026-04-17T03:39:25Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/138762025-10-24T10:39:03Zcom_2072_378070com_2072_378040col_2072_378092

2025-10-24T10:39:03Z urn:hdl:11351/13876 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 Mall, Marcus Wainwright, Claire Legg, Julian Chilvers, Mark Dittrich, Anna-Maria Gartner, Silvia 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 Children; Cystic fibrosis; Mutation Nens; Fibrosi quística; Mutació Niños; Fibrosis quística; Mutación Background: 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). 2025-10-24T10:39:03Z 2025-10-24T10:39:03Z 2025-10-16T07:26:38Z 2025-10-16T07:26:38Z 2025 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://hdl.handle.net/11351/13876 European Respiratory Journal;66(1) https://doi.org/10.1183/13993003.02435-2024 Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess European Respiratory Society Scientia