Authors: Marcus A. Mall, Claire E. Wainwright, Julian Legg, Mark Chilvers, Sylvia Gartner, Anna-Maria Dittrich, Florian Stehling, Sarah Conner, Sebastian Grant, Nina Suresh, Tanya G. Weinstock, Jane C. Davies
Published: 2025-04-10
DOI: 10.1183/13993003.02435-2024
Source: Full article
AimsElexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was efficacious and safe in children aged 6–11 years with cystic fibrosis (CF) heterozygous forF508deland a minimal functionCFTRvariant (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.MethodsIn 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.ResultsA 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).ConclusionsELX/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)