A Study to Evaluate the Safety of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

Study Overview
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Brief Summary
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This is a Phase 3, 2-arm, multicenter study with an open-label ivacaftor arm and an observational arm to evaluate the safety and efficacy of long-term ivacaftor treatment in subjects with cystic fibrosis (CF) who are <24 months of age at treatment initiation and have an approved Ivacaftor-Responsive mutation

Official Title
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A Phase 3, 2-Arm, Open-label Study to Evaluate the Safety and Pharmacodynamics of Long-term Ivacaftor Treatment in Subjects With Cystic Fibrosis Who Are Less Than 24 Months of Age at Treatment Initiation and Have an Approved Ivacaftor-Responsive Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Ivacaftor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ivacaftor Arm: Subjects From Study 124 (NCT02725567 ) Part B: Subjects transitioning from Study 124 Part B must have completed the last study visit of Study 124 Part B. As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the informed consent form (ICF). Ivacaftor Arm: Subjects Not From Study 124 Part B: Confirmed diagnosis of CF, or 2 CF-causing mutations. An ivacaftor- responsive CFTR mutation on at least 1 allele. Subjects will be eligible in countries/regions where ivacaftor is approved for use in subjects 2 years of age and older. As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions; and must sign the ICF. Observational Arm: Received ivacaftor treatment in Study 124 Part B and elected not to enroll or ineligible to enroll in the ivacaftor arm of Study 126. Exclusion Criteria: Ivacaftor Arm: Subjects From Study 124 Part B: History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the subject. Subjects receiving commercially available ivacaftor treatment Ivacaftor Arm: Subjects Not From Study 124 Part B: History of any illness or condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering ivacaftor to the subject An acute upper or lower respiratory infection, or pulmonary exacerbation, or changes in therapy for pulmonary disease within 4 weeks of Day 1 Abnormal liver function at screening Hemoglobin <9.5 g/dL at screening History of solid organ or hematological transplantation Use of any moderate or strong inducers or inhibitors of CYP3A within 2 weeks of Day 1 Observational Arm: Receiving ivacaftor treatment Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 0 Months
Maximum Age: 24 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ivacaftor Arm<br> | Drug: Ivacaftor<br>* Ivacaftor will be administered every 12 hours (q12h) from Day 1 through the morning dose of the Week 96 Visit.<br>* Other names: VX-770;|
| No Intervention: Observational Arm<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety assessments based on the number of subjects with adverse events (AEs) and serious adverse events (SAEs) | Number of subjects with AEs and SAEs will be reported. | from baseline through safety follow-up (up to 24 weeks after last dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute change in sweat chloride |  | from baseline through Week 96 |