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 of orally administered ivacaftor in subjects with CF from Study 110, Study 111, and Study 113. We are not participating in the 113 study at this site, therefore all procedures referencing this study are not applicable.
-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.
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)
observational arm endpoint
Safety, as determined by serious adverse events
inhaled Hypertoninc Saline Substudy
Subjects in the ivacaftor arm who have not taken inhaled HS for at least 4 weeks, are clinically stable, and are exacerbation free will have the option to participate in the inhaled HS substudy, which is comprised of 8 weeks of concomitant inhaled HS treatment followed by 4 weeks of no inhaled HS treatment. These subjects will have 4 substudy visits.
* HS Visit a (start of 8-week use of inhaled HS) should coincide with any regularly scheduled study visit from Week 12 through Week 84.
* HS Visit B will occur 4 ((+-) 1) weeks after HS Visit a.
* HS Visit C (end of 8-week use of inhaled HS [last dose on the evening before HS Visit C] and start 4 weeks off inhaled HS) will occur 4 ((+-) 1) weeks after HS Visit B.
* HS Visit D (end of 4 weeks off inhaled HS) should coincide with any regularly scheduled study visit and will occur approximately 4 weeks after HS Visit C.
The inhaled HS substudy will not have an early Termination Visit for subjects who prematurely discontinue the substudy. a subject who prematurely discontinues the inhaled HS substudy will continue with the regularly scheduled study visits as shown in Table 3-1.
1. Subjects from Study 110 and Study 111 entering the ivacaftor arm must have completed the assigned study drug treatment duration in the previous study.
2. Subjects from Study 113 entering the ivacaftor arm must have completed all study-related treatments through the Follow-up Visit and have met at least 1 of the following Study 113 responder criteria during the 8-week Open-label Period in that study.
* an increase in percent predicted FEV1 (absolute change) of >=5% at 1 or more timepoints
* a decrease in sweat chloride concentration of >=15 mmol/L
* an increase in the CFQ-R respiratory domain of >=4 points
* an increase in BMI of >=0.5 kg/m2
Increase and decrease are calculated from the Study 113 8-week Open-label Period baseline.
3. Subjects entering the observational arm (from Study 110 and Study 111 only) must have completed at least 4 weeks of study drug treatment in their previous study, must have completed the previous study but do not wish to enroll in the ivacaftor arm, or must have completed the previous study but do not meet the inclusion criteria of the ivacaftor arm.
4. Female subjects of childbearing potential entering the ivacaftor arm must have a negative urine pregnancy test on Day 1
5. Able to understand and comply with protocol requirements, restrictions, and instructions and likely to complete the study as planned, as judged by the investigator
6. 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 requirements
7. Subjects must sign the informed consent form (ICF), and where appropriate, assent must be obtained.