A Phase 2 Study to Evaluate Efficacy and Safety of VX-561 in Subjects Aged 18 Years and Older With Cystic Fibrosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy, safety, pharmacodynamic (PD) and pharmacokinetic (PK) effect of VX-561.

Official Title
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A Phase 2, Randomized, Double-blind Study to Evaluate the Efficacy and Safety of VX-561 in Subjects Aged 18 Years and Older With Cystic Fibrosis

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: VX-561
* Drug: IVA
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Must have 1 of the following 9 CFTR mutations on at least 1 allele: G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P, or G1349D On ivacaftor therapy FEV1 value ≥40% and ≤100% of predicted mean for age, sex, and height Key Exclusion Criteria: History of clinically significant cirrhosis with or without portal hypertension History of solid organ or hematological transplantation Lung infection with organisms associated with a more rapid decline in pulmonary status Other protocol defined Inclusion/Exclusion criteria may apply

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 |
| --- | --- |
| Active Comparator: Ivacaftor<br>Participants received IVA 150 milligrams (mg) orally every 12 hours (q12h) in the treatment period for 12 weeks. | Drug: IVA<br>* 150-mg film-coated tablet for oral administration.<br>* Other names: Ivacaftor;Drug: Placebo<br>* Placebos matched to VX-561.<br>|
| Experimental: VX-561: 25 mg<br>Participants received VX-561 25 mg orally daily (qd) in the treatment period for 12 weeks. | Drug: VX-561<br>* VX-561 tablets for oral administration.<br>* Other names: Deutivacaftor (D-IVA);Drug: Placebo<br>* Placebo matched to IVA.<br>|
| Experimental: VX-561: 50 mg<br>Participants received VX-561 50 mg orally qd in the treatment period for 12 weeks. | Drug: VX-561<br>* VX-561 tablets for oral administration.<br>* Other names: Deutivacaftor (D-IVA);Drug: Placebo<br>* Placebo matched to IVA.<br>|
| Experimental: VX-561: 150 mg<br>Participants received VX-561 150 mg orally qd in the treatment period for 12 weeks. | Drug: VX-561<br>* VX-561 tablets for oral administration.<br>* Other names: Deutivacaftor (D-IVA);Drug: Placebo<br>* Placebo matched to IVA.<br>|
| Experimental: VX-561: 250 mg<br>Participants received VX-561 250 mg orally qd in the treatment period for 12 weeks. | Drug: VX-561<br>* VX-561 tablets for oral administration.<br>* Other names: Deutivacaftor (D-IVA);Drug: Placebo<br>* Placebo matched to IVA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) | FEV1 is the volume of air that can forcibly be blown out in one second, after full inspiration. | From Baseline at Week 12 | 

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 at Week 12 | 
| Observed Pre-Dose Concentration (Ctrough) of VX-561 and Its Metabolites (M1-VX-561 and M6-VX-561) and IVA and Its Metabolites (M1-IVA and M6-IVA) |  | At Week 4 | 
| Safety and Tolerability as Assessed by Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | Baseline up to Week 16 |