A Phase 3 Study of VX-445 Combination Therapy in Cystic Fibrosis (CF) Subjects Heterozygous for F508del and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

Study Overview
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Brief Summary
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This study will evaluate the efficacy, safety and pharmacodynamics of elexacaftor (ELX, VX-445) in triple combination (TC) with tezacaftor (TEZ) and ivacaftor (IVA) in subjects with cystic fibrosis (CF) who are heterozygous for F508del and a gating or residual function mutation (F/G and F/RF genotypes).

Official Title
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A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-445 Combination Therapy in Subjects With Cystic Fibrosis Who Are Heterozygous for the F508del Mutation and a Gating or Residual Function Mutation (F/G and F/RF Genotypes)

Conditions
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Cystic Fibrosis

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject has a confirmed diagnosis of CF and is heterozygous for F508del and either a gating or residual function mutation (F/G and F/RF genotypes) Forced expiratory volume in 1 second (FEV1) value ≥40% and ≤90% of predicted mean for age, sex, and height Key Exclusion Criteria: Clinically significant cirrhosis with or without portal hypertension Lung infection 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: 12 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 |
| --- | --- |
| Active Comparator: Control: IVA or TEZ/IVA<br>Following an IVA or TEZ/IVA run-in period of 4 weeks, participants either received IVA 150 milligrams (mg) every 12 hours (q12h) or TEZ 100 mg once daily (qd)/IVA 150 mg q12h in the treatment period for 8 weeks. | Drug: IVA<br>* Mono-tablet for oral administration.<br>* Other names: ivacaftor;Drug: TEZ/IVA<br>* Fixed-dose combination (FDC) tablet for oral administration.<br>* Other names: tezacaftor/ivacaftor;|
| Experimental: TC: ELX/TEZ/IVA<br>Following an IVA or TEZ/IVA run-in period of 4 weeks, participants received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 8 weeks. | Drug: ELX/TEZ/IVA<br>* FDC tablet for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Mono-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 |
| --- | --- | --- |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) for ELX/TEZ/IVA Group | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | From Baseline Through Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Sweat Chloride (SwCl) for ELX/TEZ/IVA Group | Sweat samples were collected using an approved collection device. | From Baseline Through Week 8 | 
| Absolute Change in ppFEV1 for the ELX/TEZ/IVA Group Compared to the Control Group | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | From Baseline Through Week 8 | 
| Absolute Change in SwCl for ELX/TEZ/IVA Group Compared to the Control Group | Sweat samples were collected using an approved collection device. | From Baseline Through Week 8 | 
| Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain Score for ELX/TEZ/IVA Group | 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 | 
| Absolute Change in CFQ-R Respiratory Domain Score for ELX/TEZ/IVA Group Compared to the Control Group | 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 by Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |  | Day 1 up to Week 12 |