A Study to Evaluate the Safety and Efficacy of Long-term Treatment With TEZ/IVA in CF Subjects With an F508del CFTR Mutation

Study Overview
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Brief Summary
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This study will evaluate the long-term safety and tolerability of tezacaftor in combination with ivacaftor (TEZ/IVA) in subjects with cystic fibrosis (CF) aged 6 years and older, homozygous or heterozygous for the F508del mutation.

Official Title
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A Phase 3, Open-label, Rollover Study to Evaluate the Safety and Efficacy of Long-term Treatment With Tezacaftor in Combination With Ivacaftor in Subjects With Cystic Fibrosis Aged 6 Years and Older, Homozygous or Heterozygous for the F508del-CFTR Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: TEZ/IVA
* Drug: IVA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Completed the Week 24 Visit in Study 113 Part B or the Week 8 Visit in Study 115. Eligible CFTR Mutation. Exclusion Criteria: Pregnant and nursing females. History of poor compliance with study drug and/or procedures in a previous study as deemed by the investigator. Ongoing participation in another study with investigational drug. Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEZ/IVA<br>TEZ 50 mg once daily (qd)/IVA 75 mg every 12 hours (q12h) or TEZ 100 mg qd/IVA 150 mg q12h based on body weight for participants aged 6 through 11 years at enrollment and TEZ 100 mg qd/IVA 150 mg q12h for participants aged >=12 years at enrollment. Doses were adjusted upward for changes in body weight and/or age. | Drug: TEZ/IVA<br>* Fixed-dose combination tablet for oral administration.<br>* Other names: tezacaftor/ivacaftor;Drug: IVA<br>* Tablet for oral administration.<br>* Other names: ivacaftor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Part A: Day 1 up to Week 100 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Absolute Change in Lung Clearance Index2.5 (LCI2.5) for 115/116 FAS (TEZ/IVA Group) | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | From Parent Study 115 Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in LCI2.5 for 113B/116 LCI FAS | LCI2.5 represents the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting value. | From Parent Study 113B Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in Sweat Chloride for 115/116 FAS (TEZ/IVA Group) | Sweat samples were collected using an approved collection device. | From Parent Study 115 Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in SwCl for 113B/116 FAS | Sweat samples were collected using an approved collection device. | From Parent Study 113B Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for 115/116 FAS (TEZ/IVA Group) | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. | From Parent Study 115 Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in CFQ-R Respiratory Domain Score for 113B/116 FAS | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with CF. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. | From Parent Study 113B Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in Body Mass Index (BMI) for 115/116 FAS (TEZ/IVA Group) | BMI was defined as weight in kilograms (kg) divided by squared height in meters (m^2). | From Parent Study 115 Baseline at Week 96 (Study 116) | 
| Part A: Absolute Change in BMI for 113B/116 FAS | BMI was defined as weight in kg divided by m^2. | From Parent Study 113B Baseline at Week 96 (Study 116) |