Roll-Over Study of Ivacaftor in Cystic Fibrosis Pediatric Subjects With a CF Transmembrane Conductance Regulator Gene (CFTR) Gating Mutation

Study Overview
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Brief Summary
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The purpose of this study is to provide information regarding the long-term safety and pharmacodynamics of ivacaftor treatment in the pediatric population younger than 6 years of age with Cystic Fibrosis (CF) who have a CFTR gating mutation in at least 1 allele and will further explore the efficacy of long-term ivacaftor treatment in this population of patients with CF.

Official Title
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A Phase 3, 2-Arm, Roll-Over Study to Evaluate the Long-term Safety and Pharmacodynamics of Ivacaftor Treatment in Pediatric Subjects With Cystic Fibrosis and a CFTR Gating 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): Completed the last study visit of the treatment period of the previous study (NCT01705145) Hematology, serum chemistry, and vital signs results on Day 1 with no clinically significant abnormalities that would interfere with the study assessments, as judged by the investigator As judged by the investigator, parent or legal guardian must be able to understand protocol requirements, restrictions, and instructions and the parent or legal guardian should be able to ensure that the subject assents to participation in the study to the degree the subject can assent, and that the subject will comply with and is likely to complete the study as planned Inclusion Criteria (Observational Arm): 1. Subjects who completed their assigned study drug treatment in the previous study (NCT01705145) and elected not to enroll in the ivacaftor arm and subjects who prematurely discontinued treatment in the previous study and received at least 1 dose of study drug treatment in the previous study will be eligible for enrollment in the observational arm. Exclusion Criteria (Ivacaftor Arm): Subjects who prematurely discontinued from the previous study 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 study drug to the subject Subjects with a history of study treatment intolerance as observed in their previous study that, in the opinion of the investigator, might pose an additional risk in administering study drug to the subject Subjects receiving commercially-available ivacaftor treatment Subject was unable to complete an adequate slit-lamp examination at the last ophthalmologic examination in the previous study Exclusion Criteria: (Observational Arm) 1. Subjects receiving ivacaftor treatment will not be eligible for enrollment in the observational arm.

Ages Eligible for Study
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Minimum Age: 2 Years

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 |
| --- | --- |
| No Intervention: Observational Arm<br> | |
| Experimental: Ivacaftor<br>Ivacaftor will be administered every 12 hours (q12h) from Day 1 through the Week 84 Visit. The ivacaftor dose will be: 50 mg q12h for subjects 2 to <6 years of age and <14 kg, 75 mg q12h for subjects 2 to <6 years of age and ≥ 14 kg, or 150 mg q12h for subjects ≥ 6 years of age. | Drug: Ivacaftor<br> <br> * Other names: Kalydeco;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any untoward medical occurrence in a participant during the study; the event does not necessarily have a causal relationship with the treatment. This includes any newly occurring event or previous condition that has increased in severity or frequency after the informed consent form is signed. AE includes serious as well as Non-serious AEs. SAE (subset of AE): medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, Inpatient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. AEs with start date or increased severity on or after the first dose of study drug through the end of study participation was considered treatment-emergent. | Day 1 up to Week 97 (for participants who completed study drug dosing); Day 1 up to 24 weeks after the last dose (up to Week 108, for participants who prematurely discontinued study drug dosing) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline of Parent Study in Sweat Chloride at Week 24, 48, 72 and 84 | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of greater than or equal to (>=) 15 microliter was required for determination of sweat chloride. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). | Baseline (study 108), Week 24, 48, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Study 109 in Sweat Chloride at Week 24, 48, 72 and 84 | Sweat samples were collected using an approved Macroduct (Wescor, Logan, Utah) collection device. A volume of >=15 microliter was required for determination of sweat chloride. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). | Baseline (study 109), Week 24, 48, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Parent Study in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145) | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Study 109 in Weight at Week 12, 24, 36, 48, 60, 72 and 84 | Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Parent Study in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Study 109 in Stature at Week 12, 24, 36, 48, 60, 72 and 84 | Stature was measured as height if children could stand unassisted and follow directions; otherwise, stature was measured as length. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Parent Study in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline was defined as the most recent measurement prior to intake of the first dose of study drug in study 108 Part B (NCT01705145). | Baseline (study 108), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 
| Absolute Change From Baseline of Study 109 in Body Mass Index (BMI) at Week 12, 24, 36, 48, 60, 72 and 84 | BMI = (Weight [in kg]) divided by (Stature [in meters]) ^2. Baseline is defined as the most recent measurement prior to intake of the first dose of study drug in study 109 (NCT01946412). | Baseline (study 109), Week 12, 24, 36, 48, 60, 72 and 84 (study 109) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cystic Fibrosis