A Study Evaluating Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Subjects 6 Through 11 Years of Age With Cystic Fibrosis and F/MF Genotypes

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of elexacaftor (ELX) / tezacaftor (TEZ) / ivacaftor (IVA) triple combination (TC) in subjects 6 through 11 years of age with cystic fibrosis (CF) who are heterozygous for F508del and a minimal function (MF) mutation (F/MF genotypes).

Official Title
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A Phase 3b, Randomized, Placebo-controlled Study Evaluating the Efficacy and Safety of Elexacaftor/Tezacaftor/Ivacaftor in Cystic Fibrosis Subjects 6 Through 11 Years of Age Who Are Heterozygous for the F508del Mutation and a Minimal Function Mutation (F/MF)

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: Heterozygous for the F508del mutation (F/MF) Forced expiratory volume in 1 second (FEV1) value greater than equal to(≥) 70% 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo matched to ELX/TEZ/IVA and placebo matched to IVA in the treatment period for 24 weeks. | Other: Placebo (matched to ELX/TEZ/IVA)<br>* Placebo matched to ELX/TEZ/IVA for oral administration once daily (qd) in the morning.<br>Other: Placebo (matched to IVA)<br>* Placebo matched to IVA for oral administration qd in the evening.<br>|
| Experimental: ELX/TEZ/IVA<br>Participants weighing less than (<) 30 kilograms (kg) at screening received ELX 100 mg qd/TEZ 50 mg qd/IVA 75 mg every 12 hours (q12h) and participants weighing greater than equals to (>=) 30 kg at screening received ELX 200 mg qd/TEZ 100 mg qd/IVA 150 mg q12h in the treatment period for 24 weeks. | Drug: ELX/TEZ/IVA<br>* Fixed-dose combination tablet for oral administration qd in the morning.<br>* Other names: elexacaftor/tezacaftor/ivacaftor;Drug: IVA<br>* Tablet for oral administration qd in the evening.<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 Lung Clearance Index 2.5 (LCI2.5) | The LCI2.5 index is the number of lung turnovers required to reduce the end tidal inert gas concentration to 1/40th of its starting values and is calculated by dividing the sum of exhaled tidal breaths (cumulative exhaled volume (CEV)) by simultaneously measured functional residual capacity (FRC). An LCI of 7.5 and below is normal; values greater than 7.5 are abnormal. LCI is able to detect abnormalities in lung function earlier than more traditional modalities such as spirometry. | From Baseline Through Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Sweat Chloride (SwCl) | Sweat samples were collected using an approved collection device. | From Baseline Through Week 24 | 
| 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 28 |