Study design (if review, criteria of inclusion for studies)
Phase 3, open-label, two-part study
Participants
Children with CF aged 2-5 years and at Least One F508del Allele
Interventions
Children weighing <14 kg (on Day 1) received ELX 80 mg once daily (qd), TEZ 40 mg qd, and IVA 60 mg each morning and 59.5 mg each evening; children weighing 14 kg received ELX 100 mg qd, TEZ 50 mg qd, and IVA 75 mg every 12 hours.
Outcome measures
The primary endpoints for part A (15-d treatment period) were pharmacokinetics and safety and tolerability. For part B (24-wk treatment period), the primary endpoint was safety and tolerability; secondary endpoints included pharmacokinetics and absolute changes from baseline in sweat chloride concentration and lung clearance index(2.5) (LCI(2.5), defined as the number of lung turnovers required to reduce the end tidal N(2) concentration to 2.5% of its starting value) through Week 24.
Main results
Analysis of pharmacokinetic data from 18 children enrolled in part A confirmed the appropriateness of the part B dosing regimen. In part B, 75 children (F508del/minimal function genotypes, nâ=â52; F508del/F508del genotype, nâ=â23) were enrolled and dosed. Seventy-four children (98.7%) had adverse events, which were all mild (62.7%) or moderate (36.0%) in severity. The most common adverse events were cough, fever, and rhinorrhea. Decreases in sweat chloride concentration (-57.9 mmol/L; 95% confidence interval [CI], -61.3 to -54.6; nâ=â69) and LCI(2.5) (-0.83 U; 95% CI, -1.01 to -0.66; nâ=â50) were observed from baseline through Week 24. Mean body mass index was within the normal range at baseline and remained stable at Week 24.
Authors' conclusions
In this open-label study in children 2-5 years of age, ELX/TEZ/IVA treatment was generally safe and well tolerated, with a safety profile consistent with that observed in older age groups, and led to clinically meaningful reductions in sweat chloride concentration and LCI(2.5).