Evaluation of Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor (ELX/TEZ/IVA) in Cystic Fibrosis Subjects Without an F508del Mutation

Study Overview
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Brief Summary
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This study will evaluate the efficacy, pharmacodynamics (PD) and safety of ELX/TEZ/IVA in participants 6 years of age and older with a non-F508del ELX/TEZ/IVA-responsive cystic fibrosis transmembrane conductance regulator gene (CFTR) mutation.

Official Title
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A Phase 3 Double-blind, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of ELX/TEZ/IVA in Cystic Fibrosis Subjects 6 Years of Age and Older With a Non-F508del ELX/TEZ/IVA-responsive CFTR Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: ELX/TEZ/IVA
* Drug: IVA
* Other: Placebo (matched to ELX/TEZ/IVA)
* Other: Placebo (matched to IVA)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participant has a qualifying ELX/TEZ/IVA-responsive CFTR mutation and does not have an exclusionary CFTR mutation Forced expiratory volume in 1 second (FEV1) value >=40% and <=100% of predicted mean for age, sex, and height Key Exclusion Criteria: History of solid organ or hematological transplantation Clinically significant cirrhosis with or without portal hypertension Lung infection with organisms associated with a more rapid decline in pulmonary status 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ELX/TEZ/IVA<br>Participants will receive ELX/TEZ/IVA in the morning and IVA in the evening. | Drug: ELX/TEZ/IVA<br>* Fixed-dose combination (FDC) tablets for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Tablet for oral administration.<br>* Other names: ivacaftor;|
| Placebo Comparator: Placebo<br>Participants will receive placebo matched to ELX/TEZ/IVA in the morning and placebo matched to IVA in the evening. | Other: Placebo (matched to ELX/TEZ/IVA)<br>* Placebo matched to ELX/TEZ/IVA for oral administration.<br>Other: Placebo (matched to IVA)<br>* Placebo matched to IVA for oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) |  | From Baseline Through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Sweat Chloride (SwCl) |  | From Baseline Through Week 24 | 
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score |  | From Baseline Through Week 24 | 
| Absolute Change in Body Mass Index (BMI) |  | From Baseline at Week 24 | 
| Absolute Change in Weight |  | From Baseline at Week 24 | 
| Number of Pulmonary Exacerbations (PEx) |  | From Baseline Through Week 24 | 
| Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 up to Week 28 |