Evaluation of VX-659/TEZ/IVA in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Study Overview
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Brief Summary
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This study will evaluate the pharmacokinetics (PK), safety, tolerability, efficacy, and pharmacodynamic effect of VX-659, tezacaftor (TEZ), and ivacaftor (IVA) when dosed in triple combination (TC) in Cystic Fibrosis (CF) subjects with F/F or F/MF genotypes. The study was discontinued after completion of Part A due to Sponsor's discretion.

Official Title
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A Phase 3 Study Evaluating the Pharmacokinetics, Safety, and Tolerability of VX-659/TEZ/IVA Triple Combination Therapy in Cystic Fibrosis Subjects 6 Through 11 Years of Age

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-659/TEZ/IVA
* Drug: IVA


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Homozygous or heterozygous for F508del mutation (F/F or F/MF genotypes) Forced expiratory volume in 1 second (FEV1) value ≥40% 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: 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VX-659/TEZ/IVA<br>Participants who received VX-659 120 milligram (mg)/TEZ 50 mg/ IVA 75 mg as fixed-dose combination (FDC) in the morning and IVA 75 mg as a mono tablet in the evening in the triple combination (TC) treatment period. | Drug: VX-659/TEZ/IVA<br>* VX-659/TEZ/IVA FDC tablet.<br>* Other names: VX-659/tezacaftor/ivacaftor;Drug: IVA<br>* IVA mono tablet.<br>* Other names: ivacaftor;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of VX-659, TEZ, and IVA |  | Day 1 and Day 15 | 
| Observed Pre-Dose Concentration (Ctrough) of VX-659, TEZ, and IVA |  | Day 8 and Day 15 | 
| Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of VX-659, TEZ, and IVA |  | Day 1 and Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) |  | Day 1 and Day 15 | 
| Observed Pre-Dose Concentration (Ctrough) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) |  | Day 8 and Day 15 | 
| Area Under the Concentration Versus Time Curve From Time 0 to 6 Hours (AUC0-6h) of TEZ Metabolite (M1-TEZ), and IVA Metabolite (M1-IVA) |  | Day 1 and Day 15 | 
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From first dose of study drug in TC treatment period up to 28 days after last dose of study drug or to the completion of study participation date, whichever occurs first (up to 6 weeks) |