An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB).



Rosenfeld, Margaret, Cunningham, Steve, Harris, William T, Lapey, Allen, Regelmann, Warren E, Sawicki, Gregory S, Southern, Kevin W ORCID: 0000-0001-6516-9083, Chilvers, Mark, Higgins, Mark, Tian, Simon
et al (show 3 more authors) (2019) An open-label extension study of ivacaftor in children with CF and a CFTR gating mutation initiating treatment at age 2-5 years (KLIMB). Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society.

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Abstract

BACKGROUND:KIWI (NCT01705145) was a 24-week, single-arm, pharmacokinetics, safety, and efficacy study of ivacaftor in children aged 2 to 5 years with cystic fibrosis (CF) and a CFTR gating mutation. Here, we report the results of KLIMB (NCT01946412), an 84-week, open-label extension of KIWI. METHODS:Children received age- and weight-based ivacaftor dosages for 84 weeks. The primary outcome was safety. Other outcomes included sweat chloride, growth parameters, and measures of pancreatic function. RESULTS:All 33 children who completed KIWI enrolled in KLIMB; 28 completed 84 weeks of treatment. Most adverse events were consistent with those reported during KIWI. Ten (30%) children had transaminase elevations >3 × upper limit of normal (ULN), leading to 1 discontinuation in a child with alanine aminotransferase >8 × ULN. Improvements in sweat chloride, weight, and body mass index z scores and fecal elastase-1 observed during KIWI were maintained during KLIMB; there was no further improvement in these parameters. CONCLUSIONS:Ivacaftor was generally well tolerated for up to 108 weeks in children aged 2 to 5 years with CF and a gating mutation, with safety consistent with the KIWI study. Improvements in sweat chloride and growth parameters during the initial 24 weeks of treatment were maintained for up to an additional 84 weeks of treatment. Prevalence of raised transaminases remained stable and did not increase with duration of exposure during the open-label extension.

Item Type: Article
Uncontrolled Keywords: KLIMB study group
Depositing User: Symplectic Admin
Date Deposited: 13 May 2019 08:40
Last Modified: 28 Nov 2019 08:28
DOI: 10.1016/j.jcf.2019.03.009
Open Access URL: https://doi.org/10.1016/j.jcf.2019.03.009
URI: http://livrepository.liverpool.ac.uk/id/eprint/3040989
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