Journal article

Publication year: 2021

Pages: 68-77

Journal: Journal of Cystic Fibrosis

Volume number: 20

Issue number: 1

ISSN: 1569-1993

eISSN: 1873-5010

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.jcf.2020.07.023

Publisher: Elsevier

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 (LCI2.5) 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 LCI2.5 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. (C) 2020 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

Harvard Citation style: Davies, J., Sermet-Gaudelus, I., Naehrlich, L., Harris, R., Campbell, D., Ahluwalia, N., et al. (2021) 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, Journal of Cystic Fibrosis, 20(1), pp. 68-77. https://doi.org/10.1016/j.jcf.2020.07.023

APA Citation style: Davies, J., Sermet-Gaudelus, I., Naehrlich, L., Harris, R., Campbell, D., Ahluwalia, N., Short, C., Haseltine, E., Panorchan, P., Saunders, C., Owen, C., & Wainwright, C. (2021). 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. Journal of Cystic Fibrosis. 20(1), 68-77. https://doi.org/10.1016/j.jcf.2020.07.023