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

Abstract

<b>Rationale:</b> 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 <i>F508del-CFTR</i> (cystic fibrosis transmembrane conductance regulator) allele, but it has not been evaluated in children <12 years of age. <b>Objectives:</b> To assess the safety, pharmacokinetics, and efficacy of ELX/TEZ/IVA in children 6 through 11 years of age with <i>F508del</i>-minimal function or <i>F508del</i>-<i>F508del</i> genotypes. <b>Methods:</b> In this 24-week open-label phase 3 study, children (<i>N</i> = 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 IVA 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). <b>Measurements and Main Results:</b> The primary endpoint was safety and tolerability. The safety and pharmacokinetic profiles of ELX/TEZ/IVA were generally consistent with those observed in older patients. The most commonly reported adverse events included 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 <i>z</i>-score increased over the 24-week treatment period when compared with the pretreatment baseline. <b>Conclusions:</b> Our results show ELX/TEZ/IVA is safe and efficacious in children 6 through 11 years of age with at least one <i>F508del-CFTR</i> allele, supporting its use in this patient population. Clinical trial registered with www.clinicaltrials.gov (NCT03691779).