Evaluation of VX-121/Tezacaftor/Deutivacaftor in Cystic Fibrosis (CF) Participants 1 Through 11 Years of Age

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the pharmacokinetics, safety, tolerability and efficacy of VX-121/tezacaftor/deutivacaftor (VX-121/TEZ/D-IVA) in CF participants with at least 1 triple combination responsive (TCR) mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene.

Official Title
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A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-121/Tezacaftor/Deutivacaftor Triple Combination Therapy in Cystic Fibrosis Subjects 1 Through 11 Years of Age

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-121/TEZ/D-IVA


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Participants with stable CF and at least 1 TCR mutation (including F508del) in the CFTR gene Key Exclusion Criteria: History of solid organ, hematological transplantation, or cancer 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 Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 1 Year
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: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: 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 for oral administration.<br>* Other names: VX-121/tezacaftor/deutivacaftor;|
| Experimental: Part B: VX-121/TEZ/D-IVA<br>Participants will receive VX-121/TEZ/D-IVA in the morning with the dose(s) to be based on the outcome of Part A. | Drug: VX-121/TEZ/D-IVA<br>* Fixed-dose combination for oral administration.<br>* Other names: VX-121/tezacaftor/deutivacaftor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part A: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites |  | From Day 1 up to Day 22 | 
| Part A: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Day 1 up to Day 50 | 
| Part B: Safety and Tolerability as Assessed by Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Day 1 up to Week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part B: Absolute Change in Sweat Chloride (SwCl) |  | From Baseline Through Week 24 | 
| Part B: Observed Pre-dose Plasma Concentration (Ctrough) of VX-121, TEZ, D-IVA, and Relevant Metabolites |  | From Day 1 up to Week 16 | 
| Part B: Drug Acceptability Assessment Using Modified Facial Hedonic Scale |  | At Day 1 and Week 24 | 
| Part B: Absolute Change in Percent Predicted Forced Expiratory Volume (ppFEV1) |  | From Baseline Through Week 24 | 
| Part B: Number of Pulmonary Exacerbation (PEx) |  | From Baseline Through Week 24 | 
| Part B: Number of CF-Related Hospitalizations |  | From Baseline Through Week 24 | 
| Part B: Absolute Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Respiratory Domain (RD) Score |  | From Baseline Through Week 24 | 
| Part B: Absolute Change in Body Mass Index (BMI) |  | From Baseline at Week 24 | 
| Part B: Absolute Change in BMI-for-age Z-score |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Weight |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Weight-for-age Z-score |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Weight-for-length |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Weight-for-length Z-score |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Height |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Height-for-age Z-score |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Length |  | From Baseline at Week 24 | 
| Part B: Absolute Change in Length-for-age Z-score |  | From Baseline at Week 24 | 
| Part B: Proportion of Participants With SwCl <60 millimole per liter (mmol/L) |  | From Baseline Through Week 24 | 
| Part B: Proportion of Participants With SwCl <30 mmol/L |  | From Baseline Through Week 24 |