A phase 3, randomized, double-blind, parallel-group study to evaluate tezacaftor/ivacaftor in people with cystic fibrosis heterozygous for F508del-CFTR and a gating mutation.

摘要: Abstract Background Tezacaftor (TEZ)/ivacaftor (IVA) is an approved CFTR modulator shown to be efficacious and generally safe well tolerated in people ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous a residual function mutation. Although previous studies IVA alone showed clinical benefits gating mutations, TEZ/IVA has not yet been evaluated Phase 3 study participants (F/gating genotypes). Here, we present results from randomized, double-blind, IVA-controlled, parallel-group, assessing efficacy, safety, pharmacokinetics (PK) F/gating genotypes. Methods Enrolled entered 4-week run-in period create stable baseline. Participants were then randomized receive 8 weeks active comparator treatment (ACTP). The primary endpoint was absolute change percent predicted forced expiratory volume 1 second (ppFEV1). Key secondary endpoints relative ppFEV1 CF Questionnaire–Revised respiratory domain score. Secondary included sweat chloride (SwCl) concentration, PK parameters, safety. All except parameters safety assessed baseline through Week 8. Results Sixty-nine (92.0%) group 75 (98.7%) completed treatment. No improvements seen efficacy at end ACTP group. significant differences any key observed between groups. SwCl concentrations decreased more versus during ACTP. profile consistent those CF. Conclusions This that dual-combination regimen demonstrated but did have significantly greater than However, as reported other studies, (NCT02412111).