A Phase 3, 2-Part, Open-Label Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of Ivacaftor in Subjects With Cystic Fibrosis Who Are 2 Through 5 Years of Age and Have a CFTR Gating Mutation (KIWI)
Ivacaftor has already been shown to be safe and effective in people with CF aged 6 years and over with at least one CFTR gating mutation. This study involved 35 children aged 2 to 5 years of age who all had at least one CFTR-gating mutation, to assess safety and dosing in this younger age group.
Subjects received Ivacaftor 50mg twice a day if they weighed less than 14 kg, or 75mg twice a day if they weighed 14 kg or more. Blood levels at these doses were equivalent to the blood levels seen in the earlier adult studies.
Sweat chloride improved significantly, with an average reduction of 46.9mmol/L; weight and BMI (body mass index) also improved significantly.
Safety appeared good overall, although 15% of subjects had a large rise in their liver function tests to more than eight times the upper limit of normal. Most of these subjects had an interruption of their study drug as a result, and one subject stopped the Ivacaftor altogether.
Overall this study suggests that Ivacaftor improves sweat chloride and weight in young children aged 2-5 years who have at least one CFTR gating mutation, but careful monitoring of liver function tests in this age group will be important. Longer term effects will be assessed in an ongoing extension study.
1 ECFS-CTN site in UK participated in this study and enrolled 3 of the patients.
Reference: Safety, pharmacokinetics, and pharmacodynamics of ivacaftor in patients aged 2-5 years with cystic fibrosis and a CFTR gating mutation (KIWI): an open-label, single-arm study. Davies J et al. Lancet Respir Med 2016 Feb; 4(2): 107-15