Work

A phase 3, double-blind, parallel-group study to evaluate the efficacy and safety of tezacaftor in combination with ivacaftor in participants 6 through 11 years of age with cystic fibrosis homozygous for F508del or heterozygous for the F508del-CFTR mutation and a residual function mutation

Year: 2020

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Background The CFTR modulator tezacaftor/ivacaftor was efficacious and generally safe and well tolerated in Phase 3 studies in participants ≥12 years of age with cystic fibrosis (CF) homozygous for the F508del-CFTR mutation or heterozygous with a residual function- CFTR mutation ( F/F or F /RF respectively). We evaluated tezacaftor/ivacaftor's efficacy and safety over 8 weeks in participants 6 through 11 years of age with these mutations. Methods Participants were randomized 4:1 to tezacaftor/ivacaftor or a blinding group (placebo for F/F , ivacaftor for F /RF). The primary endpoint was within-group change from baseline in the lung clearance index 2·5 (LCI 2·5 ) through Week 8. Secondary endpoints were change from baseline in sweat chloride (SwCl), cystic fibrosis questionnaire-revised (CFQ-R) respiratory domain score, and safety. Results Sixty-seven participants received at least one study drug dose. Of those, 54 received tezacaftor/ivacaftor ( F/F , 42; F /RF, 12), 10 placebo, and 3 ivacaftor; 66 completed the study. The within-group change in LCI 2·5 was significantly reduced (improved) by −0·51 (95% CI: −0·74, −0·29). SwCl concentration decreased (improved) by −12·3 mmol/L and CFQ-R respiratory domain score increased (improved, nonsignificantly) by 2·3 points. There were no serious adverse events (AEs) or AEs leading to tezacaftor/ivacaftor discontinuation or interruption. The most common AEs (≥10%) in participants receiving tezacaftor/ivacaftor were cough, headache, and productive cough. Conclusions Tezacaftor/ivacaftor improved lung function (assessed using LCI) and CFTR function (measured by SwCl concentration) in participants 6 through 11 years of age with F/F or F /RF genotypes. Tezacaftor/ivacaftor was safe and well tolerated; no new safety concerns were identified.

Source: Journal of Cystic Fibrosis

DOI: 10.1016/j.jcf.2020.07.023