Journal article

Publication year: 2022

Pages: 675-683

Journal: Journal of Cystic Fibrosis

Volume number: 21

Issue number: 4

ISSN: 1569-1993

eISSN: 1873-5010

Open access status: Hybrid

DOI Link: https://doi.org/10.1016/j.jcf.2022.02.003

Publisher: Elsevier

Abstract: 

Background: Two previous Phase 3 studies ("parent studies") showed that tezacaftor/ivacaftor was generally safe and efficacious for up to 24 weeks in children 6 through 11 years of age with cystic fibrosis (CF) and F508del/F508del (F/F) or F508del/residual function (F/RF) genotypes. We assessed the safety and efficacy of tezacaftor/ivacaftor in an open-label, 96-week extension study.

Methods: This was a Phase 3, 2-part, multicenter, open-label, extension study in children 6 through 11 years of age at treatment initiation (Study VX17-661-116; NCT03537651). The primary endpoint was safety and tolerability. Secondary endpoints were absolute change from baseline in lung clearance index(2.5) (LCI2.5), sweat chloride (SwCl) concentration, Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score, and body mass index (BMI).

Results: One-hundred thirty children enrolled and received >= 1 dose of tezacaftor/ivacaftor; 109 completed treatment. Most (n = 129) had >= 1 treatment-emergent adverse event (TEAE), the majority of which were mild or moderate in severity and generally consistent with common manifestations of CF. Exposure-adjusted TEAE rates were similar to or lower than those in the parent studies. Five (3.8%) had TEAEs leading to treatment discontinuation. Efficacy results from the parent studies were maintained, with improvements in lung function, SwCl concentration, CFQ-R respiratory domain score, and BMI observed from parent study baseline to Week 96.

Conclusions: Tezacaftor/ivacaftor is generally safe and well tolerated, and treatment effects are maintained for up to 120 weeks. These results support long-term use of tezacaftor/ivacaftor in children >= 6 years of age with CF and F/F or F/RF genotypes. (C) 2022 The Authors. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

Harvard Citation style: Sawicki, G., Chilvers, M., McNamara, J., Naehrlich, L., Saunders, C., Sermet-Gaudelus, I., et al. (2022) A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children ≥ 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant, Journal of Cystic Fibrosis, 21(4), pp. 675-683. https://doi.org/10.1016/j.jcf.2022.02.003

APA Citation style: Sawicki, G., Chilvers, M., McNamara, J., Naehrlich, L., Saunders, C., Sermet-Gaudelus, I., Wainwright, C., Ahluwalia, N., Campbell, D., Harris, R., Paz-Diaz, H., Shih, J., & Davies, J. (2022). A Phase 3, open-label, 96-week trial to study the safety, tolerability, and efficacy of tezacaftor/ivacaftor in children ≥ 6 years of age homozygous for F508del or heterozygous for F508del and a residual function CFTR variant. Journal of Cystic Fibrosis. 21(4), 675-683. https://doi.org/10.1016/j.jcf.2022.02.003