A Phase 3 Open-Label Study of Elexacaftor/Tezacaftor/lvacaftor in Children 6 through 11 Years of Age with Cystic Fibrosis and at Least One F508del Allele

Rationale: Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) was shown to be efficacious and safe in patients >= 12 years of age with cystic fibrosis and at least one F508del-CFTR (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. Objectives: To assess the safety, pharmacokinetics, and efficacy of ELX/TEVIVA in children 6 through 11 years of age with F508del-minimal function or F508del-F508del genotypes. Methods: In this 24-week open-label phase 3 study, children (N = 66) weighing <30 kg received 50% of the ELX/TEZ/IVA adult daily dose (ELX 100 mg once daily, TEZ 50 mg once daily, and WA 75 mg every 12 h) whereas children weighing >= 30 kg received the full adult daily dose (ELX 200 mg once daily, TEZ 100 mg once daily, and IVA 150 mg every 12 h). Measurements and Main Results: The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events induded cough, headache, and pyrexia; in most of the children who had adverse events, these were mild or moderate in severity. Through Week 24, ELX/TEZ/IVA treatment improved the percentage of predicted FEV1 (10.2 percentage points; 95% confidence interval [CI], 7.9 to 12.6), Cystic Fibrosis Questionnaire-Revised respiratory domain score (7.0 points; 95% CI, 4.7 to 9.2), lung clearance index 2 . 5 (-1.71 units; 95% CI, - 2.11 to -1.30), and sweat chloride (-60.9 mmol/L; 95% CI, - 63.7 to -58.2); body mass index-for-age z-score increased over the 24-week treatment period when compared with the pretreatment baseline. Conclusions: Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one F508del-CFTR allele, supporting its use in this patient population.

Automated summary

Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) has been shown to be safe and efficacious in children aged 6 through 11 with at least one F508del-CFTR allele, supporting its use in this patient population. The treatment improved lung function, respiratory scores, lung clearance, sweat chloride levels, and body mass index in these children over the 24-week period. The safety and pharmacokinetic profiles were consistent with those observed in older patients.