A Study to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

Study Overview
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Brief Summary
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This study will explore the impact of lumacaftor/ivacaftor (LUM/IVA) on disease progression in subjects aged 2 through 5 years with cystic fibrosis (CF), homozygous for F508del (F/F).

Official Title
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An Exploratory Phase 2, 2-part, Randomized, Double-blind, Placebo-controlled Study With a Long-term, Open-label Period to Explore the Impact of Lumacaftor/Ivacaftor on Disease Progression in Subjects Aged 2 Through 5 Years With Cystic Fibrosis, Homozygous for F508del

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: LUM/IVA
* Drug: LUM/IVA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subjects with confirmed diagnosis of CF. Homozygous for F508del (F/F). Subjects who weigh ≥8 kg without shoes and wearing light clothing at the Screening Visit. Key Exclusion Criteria: Any clinically significant laboratory abnormalities at the Screening Visit that would interfere with the study assessments or pose an undue risk for the subject. Solid organ or hematological transplantation. History of any illness or comorbidity reviewed at the Screening Visit that, in the opinion of the investigator, might confound the results of the study. Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 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: Part 1: Placebo<br>Participants received placebo matched to LUM/IVA in placebo-controlled period for 48 weeks. | Drug: Placebo<br>* Placebo matched to LUM/IVA for oral administration.<br>|
| Experimental: Part 1: LUM/IVA<br>Participants weighing less than (<)14 kilograms (kg) at screening received LUM 100 milligrams (mg)/IVA 125 mg fixed-dose combination (FDC) every 12 hours (q12h) in placebo-controlled period for 48 weeks. Participants weighing greater than or equals to (>=)14 kg at screening received LUM 150 mg/IVA 188 mg FDC q12h in placebo-controlled period for 48 weeks. | Drug: LUM/IVA<br>* FDC granules for oral administration.<br>* Other names: VX-809/VX-770;|
| Experimental: Part 2: Overall LUM/IVA<br>Participants who received either placebo or LUM/IVA in placebo-controlled period administered LUM/IVA (either LUM 100 mg/IVA 125 mg FDC q12h or LUM 150 mg/IVA 188 mg FDC q12h as per their body weight for participants <6 years of age at week 48 and LUM 200 mg/IVA 250 mg FDC q12h regardless of their body weight for participants >=6 years of age at week 48) in open-label period for 48 weeks. | Drug: LUM/IVA<br>* FDC tablets or granules for oral administration.<br>* Other names: VX-809/VX-770;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Absolute Change From Baseline in MRI Global Chest Score at Week 48 | MRI scans assessed semi-quantitatively via a standardized chest MRI scoring system. Each participant had 6 lobes scored using 7 scoring parameters:1) Bronchiectasis/wall thickening 2) Mucus plugging 3) Abscesses/sacculations 4) Consolidations 5) Special findings 6)Mosaic pattern 7) Perfusion abnormalities. For each of 7 parameter, there were scores of 6 lobes (score of each lobe : 0= normal value, 1 = <50% of lobe involved and 2 = >=50% of lobe involved). MRI global score was calculated as sum of parameters 1 to 7. MRI total score is ranged from 0-84. Higher score indicate more lobe involvement. | From Baseline at Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Absolute Change in Lung Clearance Index2.5 (LCI2.5) Through Week 48 | LCI2.5 represents the number of lung turnovers required to reduce the end-tidal inert gas concentration to 1/40th of its starting value. | From Baseline Through Week 48 | 
| Part 1: Absolute Change in Weight-for-age Z-score at Week 48 | The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. | From Baseline at Week 48 | 
| Part 1: Absolute Change in Stature-for-age Z-score at Week 48 | The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. | From Baseline at Week 48 | 
| Part 1: Absolute Change in Body Mass Index (BMI)-For-age Z-score at Week 48 | BMI was defined as weight in kilogram (kg) divided by squared height in meters (m^2). The z-score is a statistical measure to describe whether a value was above or below the standard. A z-score of 0 is equal to the standard. Lower numbers indicate values lower than the standard and higher numbers indicate values higher than the standard. | From Baseline at Week 48 |