A Phase 3 Study of VX-121 Combination Therapy in Participants With Cystic Fibrosis (CF) Heterozygous for F508del and a Minimal Function Mutation (F/MF)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants who are heterozygous for F508del and a minimal function mutation (F/MF participants).

Official Title
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A Phase 3, Randomized, Double-blind, Controlled Study Evaluating the Efficacy and Safety of VX-121 Combination Therapy in Subjects With Cystic Fibrosis (CF) Who Are Heterozygous for F508del and a Minimal Function Mutation (F/MF)

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-121/TEZ/D-IVA
* Drug: ELX/TEZ/IVA
* Drug: IVA
* Drug: Placebo (matched to VX-121/TEZ/D-IVA)
* Drug: Placebo (matched to ELX/TEZ/IVA)
* Drug: Placebo (matched to IVA)


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Heterozygous for F508del and a minimal function mutation (F/MF genotype) Forced expiratory volume in 1 second (FEV1) value >=40% and <=90% of predicted mean for age, sex, and height for participants currently receiving ELX/TEZ/IVA therapy; FEV1 >=40% and <=80% for participants not currently receiving ELX/TEZ/IVA Key Exclusion Criteria: History of solid organ or hematological transplantation Hepatic cirrhosis with portal hypertension, moderate hepatic impairment (Child Pugh Score 7 to 9), or severe hepatic impairment (Child Pugh Score 10 to 15) Lung infection with organisms associated with a more rapid decline in pulmonary status Pregnant or breast-feeding females 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 |
| --- | --- |
| Experimental: VX-121/TEZ/D-IVA<br>Participants will receive VX-121/TEZ/D-IVA in the morning. | Drug: VX-121/TEZ/D-IVA<br>* Fixed-dose combination tablets for oral administration.<br>* Other names: VX-121/tezacaftor/deutivacaftor;Drug: Placebo (matched to ELX/TEZ/IVA)<br>* Placebo matched to ELX/TEZ/IVA for oral administration.<br>Drug: Placebo (matched to IVA)<br>* Placebo matched to IVA for oral administration.<br>|
| Active Comparator: 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 tablets for oral administration.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Tablet for oral administration.<br>* Other names: ivacaftor;Drug: Placebo (matched to VX-121/TEZ/D-IVA)<br>* Placebo matched to VX-121/TEZ/D-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 From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) Through Week 24 |  | From Baseline Through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Sweat Chloride (SwCl) Through Week 24 |  | From Baseline Through Week 24 | 
| Proportion of Participants With SwCl <60 Millimole per Liter (mmol/L) Through Week 24 (Pooled With Data From Study VX20-121-103) |  | From Baseline Through Week 24 | 
| Proportion of Participants With SwCl <30 mmol/L Through Week 24 (Pooled With Data From Study VX20-121-103) |  | From Baseline Through Week 24 |