Study to Evaluate the Safety and Efficacy of CTP-656 in Patients With Cystic Fibrosis With CFTR Gating Mutations

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of CTP-656 in patients with cystic fibrosis (CF) who have a cystic fibrosis transmembrane conductance regulator (CFTR) gating mutation.

Detailed Description
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This is a randomized, parallel-group, double-blind, placebo controlled multicenter study to evaluate the safety and efficacy of CTP-656 in CF patients with CFTR gating mutations, compared to Kalydeco, for a total of 28 days. Subjects will be randomized to receive either double-blind CTP-656 or placebo, or open-label Kalydeco.

Official Title
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A Phase 2, Randomized, Parallel-Group, Double-Blind, Placebo Controlled Study to Evaluate the Safety and Efficacy of CTP-656 With an Open-Label Active Comparator in Patients With Cystic Fibrosis With CFTR Gating Mutations.

Conditions
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Cystic Fibrosis

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years of age or older Has a confirmed diagnosis of CF with at least one allele of the following CFTR gating mutations: G551D, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, and S549R. Has been stable on Kalydeco therapy for at least 3 months prior to screening Has FEV1 ≥ 60% of predicted normal for age, sex, and height at screening and baseline (Day 1) assessments Weighs at least 40 kg at screening Patients of either gender and women of childbearing potential must be willing to use a medically highly effective form of birth control during the treatment period and 30 days after the last dose of study treatment. Exclusion Criteria: Acute upper respiratory infection or lower respiratory infection, pulmonary exacerbation, or changes in therapy within 4 weeks of study treatment Uncontrolled type 2 diabetes, or uncontrolled CF-related diabetes History of hepatitis C or chronic active hepatitis B infection History of pulmonary tuberculosis, non-tuberculosis mycobacterial infections or allergic bronchopulmonary aspergillosis (ABPA) treated during screening or within 2 years prior to screening Colonization with B. cenocepacia, B. dolosa, B. multivorans, and/or M. abcessus within 2 years prior to Screening Abnormal liver function History of abnormal renal function History of prolonged QTcF > 450 msec for males or QTcF > 470 msec for females History of solid organ or hematological transplantation Using any inhibitor or inducer of cytochrome P450/3A during the study or within 30 days of screening Women who are pregnant or lactating, or have plans to become pregnant during the study or within 1 month following the last dose

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 |
| --- | --- |
| Experimental: VX-561 20 mg<br> | Drug: VX-561<br> <br> * Other names: CTP-656;|
| Experimental: VX-561 100 mg<br> | Drug: VX-561<br> <br> * Other names: CTP-656;|
| Experimental: VX-561 150 mg<br> | Drug: VX-561<br> <br> * Other names: CTP-656;|
| Active Comparator: Ivacaftor<br> | Drug: IVA<br> <br> * Other names: Kalydeco;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Sweat Chloride at Day 28 |  | From baseline at Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Percent Predicted Forced Expiratory Volume in 1 Second (ppFEV1) at Day 28 |  | From baseline at Day 28 | 
| Change From Baseline in Cystic Fibrosis Questionnaire-Respiratory Domain (CFQ-R) at Day 28 |  | From baseline at Day 28 |