A Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

Study Overview
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Brief Summary
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The primary purpose of study is to evaluate the treatment effect of tezacaftor in combination with ivacaftor (TEZ/IVA) on chest imaging endpoints using low-dose computed tomography (LDCT) at Week 72, and to evaluate the safety of TEZ/IVA through Week 72.

Official Title
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A Phase 2, Randomized, Placebo-Controlled, Double-blind Study to Evaluate the Effect of VX-661 in Combination With Ivacaftor on Chest Imaging Endpoints in Subjects Aged 12 Years and Older With Cystic Fibrosis, Homozygous for the F508del CFTR Mutation

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Tezacaftor/Ivacaftor
* Drug: Ivacaftor
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Homozygous for the F508del CFTR mutation Confirmed diagnosis of CF Percent predicted forced expiratory volume (ppFEV1) ≥70% of predicted normal for age, sex, and height during screening. Stable CF disease as judged by the investigator Exclusion Criteria: History of any comorbidity that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. An acute upper or lower respiratory infection, pulmonary exacerbation, or changes in therapy (including antibiotics) for pulmonary disease within 28 days before Day 1 (first dose of study drug) Pregnant or nursing females. Sexually active subjects of reproductive potential who are not willing to follow the contraception requirements. Any contraindication to undergoing chest imaging, as per the site's institutional guidelines

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEZ/IVA<br>Participants received TEZ 100 milligram (mg)/IVA 150 mg fixed dose combination tablet orally once daily in the morning and IVA 150 mg tablet orally once daily in the evening for 72 weeks. | Drug: Tezacaftor/Ivacaftor<br>* TEZ 100 mg/IVA 150 mg fixed-dose combination tablet.<br>* Other names: TEZ/IVA; VX-661/VX-770;Drug: Ivacaftor<br>* IVA 150 mg tablet.<br>* Other names: VX-770; IVA;|
| Placebo Comparator: Placebo<br>Participants received placebo matched to TEZ/IVA fixed dose combination tablet orally once daily in the morning and placebo matched to IVA tablet orally once daily in the evening for 72 weeks. | Drug: Placebo<br>* Placebo matched to TEZ/IVA fixed-dose combination tablet.<br>Drug: Placebo<br>* Placebo matched to IVA tablet.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Total Brody/CF-CT Score | The exploratory Brody/CF-CT score semi-quantitatively scores the degree of structural lung disease as shown on CT in participants with CF. The score ranges from a minimum of 0 to a maximum of 219 with higher scores indicating more severe structural lung disease. | From Baseline at Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Day 1 up to Week 76 |