Ivacaftor Treatment in 1 to 2 Year Old CF Subjects

Ivacaftor is a novel FDA approved therapy for patients with CF and gating mutations who are 1
year and older. This investigator-Initiated study is designed to evaluate the nutritional,
growth and GI impact of ivacaftor treatment for the youngest (1 to 2 years) patient cohort
and for whom FDA approval has recently been granted. This proposal directly extends the
previous highly informative nutrition and weight gain investigation of ivacaftor treatment in
the older patient cohort (1). The primary aims of the study are to evaluate the impact of 12
weeks of ivacaftor treatment in 1 to 2 year old subjects with CF and gating mutations on
sleeping energy expenditure, growth status and gut health and function in 18 children with
protocol evaluations at baseline (pre-treatment) and 6 and 12 weeks after clinically
prescribed ivacaftor treatment has begun. Other outcomes of significant clinical interest in
young subjects with CF will be explored. All subjects will be evaluated at the Children's
Hospital of Philadelphia (CHOP) and will be recruited both regionally and nationally to
ensure timely enrollment.

Inclusion Criteria:

- Cystic fibrosis with at least one CFTR gating mutation of these ten (G551D, G178R,
S549N, S549R, G551S, G1244E, S1251N, S1255P, G1439D, or R117H) approved for treatment

- Age: 1 to 2 years of age

- In their usual state of good health

- A clinical decision has been made for subject to begin ivacaftor treatment

- Family committed to the 4 to 6 month study protocol with visits to CHOP that will last
2 or 3 days for the baseline visit (Visit 1) prior to ivacaftor and the 12 week visit
(Visit 3) after clinically prescribed ivacaftor treatment has begun, and will last 2
days for the 6 week visit (Visit 2) after ivacaftor treatment has begun.

- Note that if ivacaftor is approved by the FDA for 1 to 2 year old children for the
additional 28 CFTR mutations known to be responsive to ivacaftor potentiation, these
will also be considered. With our limited samples size, the mutations that have shown
the strongest improvement with treatment will be given priority for enrollment.

Exclusion Criteria:

- On parenteral nutrition

- Use of any medications which are as inhibitors or inducers of cytochrome P450 (CYP) 3A

- Liver function tests elevated above 3x the reference range for age and sex

- Other illness affecting growth or nutritional status

- Other contraindications described for ivacaftor therapy