A Study to Evaluate Efficacy and Safety of TEZ/IVA in Subjects Aged 6 Through 11 Years With Cystic Fibrosis

Study Overview
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Brief Summary
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This study will evaluate the efficacy of tezacaftor in combination with ivacaftor (TEZ/IVA) in participants with cystic fibrosis (CF) aged 6 through 11 years, who are homozygous for the F508del mutation (F/F) or heterozygous for F508del with an eligible residual function mutation (F/RF).

Official Title
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A Phase 3, Double-blind, Parallel-group Study to Evaluate the Efficacy and Safety of Tezacaftor in Combination With Ivacaftor in Subjects Aged 6 Through 11 Years With Cystic Fibrosis, 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
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Homozygous for F508del or heterozygous for F508del and an RF mutation (as defined in the protocol). Participants with ppFEV1 of ≥70 percentage points adjusted for age, sex, height. Participants with a screening LCI2.5 result ≥7.5. Participants who are able to swallow tablets. Key Exclusion Criteria: Clinically significant cirrhosis with or without portal hypertension. Colonization with organisms associated with a more rapid decline in pulmonary status. Solid organ or hematological transplantation. Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Placebo<br>Participants with genotype F/F received placebo matched to TEZ/IVA fixed dose combination (FDC) in the morning and placebo matched to IVA in the evening for 8 weeks. | Drug: Placebo<br>* Placebo matched to TEZ/IVA FDC<br>Drug: Placebo<br>* Placebo matched to IVA<br>|
| Experimental: TEZ/IVA<br>Participants with genotype F/F received TEZ/IVA FDC in the morning and IVA in the evening for 8 weeks. Participants with genotype F/RF received TEZ/IVA FDC and placebo matched to IVA in the morning and IVA in the evening for 8 weeks. | Drug: TEZ/IVA<br>* Participants weighing <40 kg received TEZ 50 mg/IVA 75 mg FDC tablet and those weighing ≥40 kg received TEZ 100 mg/IVA 150 mg FDC tablet.<br>* Other names: tezacaftor/ivacaftor fixed dose combination;Drug: IVA<br>* Participants weighing <40 kg IVA 75 mg tablet and those weighing ≥40 kg received IVA 150 mg tablet.<br>* Other names: ivacaftor;Drug: Placebo<br>* Placebo matched to IVA<br>|
| Experimental: Ivacaftor<br>Participants with genotype F/RF received placebo matched to TEZ/IVA FDC in the morning and IVA in morning and evening for 8 weeks. | Drug: IVA<br>* Participants weighing <40 kg IVA 75 mg tablet and those weighing ≥40 kg received IVA 150 mg tablet.<br>* Other names: ivacaftor;Drug: Placebo<br>* Placebo matched to TEZ/IVA FDC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Lung Clearance Index 2.5 (LCI2.5) Through Week 8 | 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 baseline through Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Sweat Chloride At Week 8 | Sweat samples were collected using an approved collection device. | From baseline at Week 8 | 
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score Through Week 8 | The CFQ-R is a validated participant-reported outcome measuring health-related quality of life for participants with cystic fibrosis. Respiratory domain assessed respiratory symptoms, score range: 0-100; higher scores indicating fewer symptoms and better health-related quality of life. | From baseline through Week 8 | 
| Safety and Tolerability as Assessed Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) up to Safety Follow-up Visit |  | From first dose of study drug up to safety follow-up visit (up to Week 12) |