The European respiratory journal · 2025
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.
СтатьяКлиническое исследование III фазыМногоцентровое исследованиеРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Mall Marcus A, Wainwright Claire E, Legg Julian, Chilvers Mark, Gartner Sylvia, Dittrich Anna-Maria, Stehling Florian, Conner Sarah, Grant Sebastian, Suresh Nina, Weinstock Tanya G, Davies Jane C, VX20-445-119 Study Group
Аннотация
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.
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.