A Phase 2 Study to Evaluate Effects of VX-661/Ivacaftor on Lung and Extrapulmonary Systems in Subjects With Cystic Fibrosis, Homozygous for the F508del-CFTR Mutation

Study Overview
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Brief Summary
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To evaluate the clinical mechanisms of action in lung and extrapulmonary systems of VX-661 (tezacaftor; TEZ) in combination with ivacaftor (IVA) (TEZ/IVA) in participants with cystic fibrosis (CF) who are homozygous for the F508del mutation on the CF transmembrane conductance regulator (CFTR) gene.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo Controlled, Parallel-Group, Exploratory Study to Evaluate Effects of VX-661 in Combination With Ivacaftor on Lung and Extrapulmonary Systems in Subjects Aged 18 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: Tezacaftor/Ivacaftor matching placebo
* Drug: Ivacaftor matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants, homozygous for the F508del CFTR mutation Confirmed diagnosis of CF by sweat chloride testing Forced Expiratory Volume in 1 Second (FEV1) ≥40% and ≤90% of predicted normal for age, sex, and height at Screening Visit 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 for pulmonary disease within 28 days before Day 1 History or evidence of clinically significant findings on ophthalmologic examination during the Screening Period. History of solid organ or hematological transplantation Pregnant or nursing females Participants who have had radiation exposure within 1 year before the first mucociliary clearance (MCC) procedure that would cause them to exceed federal regulations by participating in this study In the opinion of the investigator, unable to adequately perform inhalation maneuvers during the MCC procedures

Ages Eligible for Study
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Minimum Age: 18 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 tezacaftor (TEZ)/ivacaftor (IVA) fixed dose combination (FDC) tablet orally once daily in the morning followed by placebo matched to IVA tablet orally once daily in the evening for 29 days. | Drug: Tezacaftor/Ivacaftor matching placebo<br> <br> Drug: Ivacaftor matching placebo<br> <br> |
| Experimental: TEZ/IVA<br>Participants received 100 milligram (mg) TEZ/150 mg IVA FDC tablet orally once daily in the morning followed by 150 mg IVA tablet orally once daily in the evening for 29 days. | Drug: Tezacaftor/Ivacaftor<br>* Tezacaftor/Ivacaftor FDC<br>Drug: Ivacaftor<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Mucociliary Clearance (MCC) at Day 28 | MCC was assessed using an imaging technique that enables the tracking of mucus within the airways. MCC was expressed as the percentage of whole-lung clearance through 60 minutes at Baseline and Day 28. | Baseline, Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28 | Percent predicted FEV1 is the ratio of FEV1 to the predicted FEV1, expressed as a percentage. FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | Baseline, Day 28 | 
| Absolute Change From Baseline in Small-bowel Area Under the Curve (AUC) Over 1-minute Mean pH Increments at Day 29 | Absolute change from Baseline in small bowel AUC over 1-minute mean pH increments through 30 minutes at Day 29 was assessed. | Baseline, Day 29 | 
| Absolute Change From Baseline in Sweat Chloride at Day 29 |  | Baseline, Day 29 | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Baseline up to Day 57 |