A Phase 3, Two-Arm, Rollover Study to Evaluate the Safety of Long-Term Ivacaftor Treatment in Subjects 6 Years of Age and Older with Cystic Fibrosis and a Non-G551D CFTR Mutation
This is a Phase 3, multicenter, 2-arm study to evaluate the long-term safety and efficacy of
ivacaftor on subjects with CF who completed Study 110 (subjects with the R117H-CFTR
mutation) or Study 111 (subjects with a non-G551D-CFTR mutation).
-Ivacaftor arm: Subjects who completed assigned study drug treatment duration in the
previous study will be enrolled. The treatment duration will be Day 1 through
approximately 104 weeks. Early Termination Visit, if applicable, as soon as possible after last ivacaftor dose. Follow-up Visit 4 weeks (± 7 days) after the last ivacaftor dose for subjects who do not continue immediately on Kalydeco (commercially available ivacaftor). An Early Termination Follow-up Ophthalmologic Examination for subjects who
were aged 6 to 11 years (inclusive) at the Day 1 Visit in Study 110 and Study 111 which will be 6 months (± 2 weeks) after the last dose of study drug.
-Observational arm: Subjects who prematurely discontinued study drug treatment and
received at least 4 weeks of treatment in the previous ivacaftor study, subjects who completed the previous study and enrolled into the observational arm, and subjects who completed the previous study but did not meet the inclusion criteria of the ivacaftor arm will be enrolled. This arm will include: Day 1, an Ophthalmologic examination 6 months (± 2 weeks) after the last dose of study drug only for subjects aged 6 to 11 years (inclusive) at the start of the previous study, and Long-term Follow-up of telephone contacts at 1 year (± 4 weeks) and 2 years (± 4 weeks)
after the last dose of study drug in the previous study.
A schematic of the study design is provided in Figure 9-1. A schematic of study flow is
provided in Appendix A (Section 16).
Ivacaftor Arm Endpoints
Safety of long-term ivacaftor treatment, as determined by adverse events, clinical laboratory
values (serum chemistry and hematology), electrocardiogram (ECGs), and vital signs
The efficacy of long-term ivacaftor treatment, as determined by
- Absolute change from baseline in percent predicted forced expiratory volume in 1 second (FEV1)
- Change from baseline in body mass index (BMI)
- Change from baseline in sweat chloride
- Change from baseline in the respiratory domain of the Cystic Fibrosis Questionnaire-Revised (CFQ-R)
- Pulmonary exacerbation (see Section 12.5.5)
- Change from baseline in non-respiratory domains of the CFQ-R
- Change from baseline in weight
- Change from baseline in height
- CF-related complications (pancreatitis or distal ileal obstruction syndrome [DIOS])
- Change from baseline in inflammatory mediators
- Change from baseline in qualitative microbiolgical cultures
- Change from baseline in immunoreactive trypsinogen (IRT) for subjects who completed study drug treatment in Study 110
- Change from baseline in fecal elastase-1 for subjects who completed study drug treatment
in Study 110
Observational Arm Endpoint
Safety, as determined by serious adverse events
1. Subjects entering the ivacaftor arm must have completed the assigned study drug
treatment duration in the previous study (Study 110 or Study 111). Subjects entering the
observational arm must have completed at least 4 weeks of study drug treatment in their
previous study (Study 110 or Study 111).
2. Female subjects of childbearing potential entering the ivacaftor arm must have a negative
urine pregnancy test on Day 1.
3. Able to understand and comply with protocol requirements, restrictions, and instructions
and likely to complete the study as planned, as judged by the investigator
4. If sexually active and entering the ivacaftor arm, male subjects who can father a child and
female subjects of childbearing potential must agree to meet the contraception
5. Subjects must sign the informed consent form (ICF), and where appropriate, assent must