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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
Abstract
Aims
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 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 (qd), TEZ 50?mg qd, and IVA 75?mg every 12?h (q12) and children ?30?kg or ?12?years receiving ELX 200?mg qd, TEZ 100?mg qd, and IVA 150?mg q12. Primary endpoint was safety and tolerability. Secondary and other efficacy endpoints included absolute changes from parent study baseline in sweat chloride concentration, LCI2.5, ppFEV1, and CFQ-R respiratory domain score.
Results
A total of 120 children were enrolled and dosed. One hundred and eighteen 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), ppFEV1 (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 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 pediatric population. (Clinical Trials.gov, NCT04545515; EudraCT, 2020-001404-42)
sumber : https://publications.ersnet.org/content/erj/early/2025/03/06/1399300302435-2024
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