A phase 3 study of tezacaftor in combination with ivacaftor in children aged 6 through 11 years with cystic fibrosis
Seth Walker, Patrick Flume, John McNamara, Melinda Solomon, Mark Chilvers, James Chmiel, R Scott Harris, Eric Haseltine, David Stiles, Chonghua Li, Neil Ahluwalia, Honghong Zhou, Caroline A Owen, Gregory Sawicki, VX15-661-113 Investigator Group, Seth Walker, Patrick Flume, John McNamara, Melinda Solomon, Mark Chilvers, James Chmiel, R Scott Harris, Eric Haseltine, David Stiles, Chonghua Li, Neil Ahluwalia, Honghong Zhou, Caroline A Owen, Gregory Sawicki, VX15-661-113 Investigator Group
Abstract
Background: Tezacaftor/ivacaftor is a new treatment option in many regions for patients aged ≥12 years who are homozygous (F/F) or heterozygous for the F508del-CFTR mutation and a residual function (F/RF) mutation. This Phase 3, 2-part, open-label study evaluated the pharmacokinetics (PK), safety, tolerability, and efficacy of tezacaftor/ivacaftor in children aged 6 through 11 years with these mutations.
Methods: Part A informed weight-based tezacaftor/ivacaftor dosages for part B. The primary objective of part B was to evaluate the safety and tolerability of tezacaftor/ivacaftor through 24 weeks; the secondary objective was to evaluate efficacy based on changes from baseline in percentage predicted forced expiratory volume in 1 s (ppFEV1), growth parameters, sweat chloride, and the Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score.
Results: After PK analysis in part A, 70 children received ≥1 dose of tezacaftor/ivacaftor in part B; 67 children completed treatment. Exposures in children aged 6 through 11 years were within the target range for those observed in patients aged ≥12 years. The safety profile of tezacaftor/ivacaftor was generally similar to prior studies in patients aged ≥12 years. One child discontinued treatment for a serious adverse event of constipation. Tezacaftor/ivacaftor treatment improved sweat chloride levels and CFQ-R respiratory domain scores, mean ppFEV1 remained stable in the normal range, and growth parameters remained stable over 24 weeks.
Conclusions: Tezacaftor/ivacaftor was generally safe and well tolerated, and improved CFTR function in children aged 6 through 11 years with CF with F/F and F/RF genotypes, supporting tezacaftor/ivacaftor use in this age group. NCT02953314.
Keywords: Cystic fibrosis; Ivacaftor; Tezacaftor.
Copyright © 2019. Published by Elsevier B.V.
Source: PubMed