A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-135 and Daclatasvir in Subjects With Genotype 1 Chronic Hepatitis C Chronic Hepatitis C

Study Overview
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Brief Summary
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A Phase 2 Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-135 and Daclatasvir in Treatment-Naïve Adult Subjects With Genotype 1 Chronic Hepatitis C

Official Title
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A Phase 2, Multicenter, Randomized, Partially-Blind, Dose-Ranging Study to Evaluate the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of VX-135 and Daclatasvir in Treatment-Naïve Adult Subjects With Genotype 1 Chronic Hepatitis C

Conditions
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Chronic Hepatitis C, CHC, HCV, Hepatitis C

Intervention / Treatment
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* Drug: VX-135
* Drug: Daclatasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have genotype 1 CHC and evidence of HCV infection at least 6 months before screening Subjects must be treatment-naïve and have not received prior treatment with any interferon, immunomodulatory agent, or DAA for HCV Exclusion Criteria: Evidence of cirrhosis History or other clinical evidence of significant or unstable cardiac disease Any other cause of significant liver disease in addition to hepatitis C Creatinine clearance ≤50 mL/min using the Cockcroft-Gault equation at screening Female subjects who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VX-135 High Dose with Daclatasvir<br>12 weeks of a high dose of VX-135 in combination with Daclatasvir | Drug: VX-135<br> <br> Drug: Daclatasvir<br> <br> |
| Experimental: VX-135 Low Dose with Daclatasvir<br>12 weeks of a low dose of VX-135 in combination with Daclatasvir | Drug: VX-135<br> <br> Drug: Daclatasvir<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability as assessed by adverse events (AEs), vital signs, 12-lead electrocardiograms (ECGs), echocardiograms, and laboratory assessments |  | Up to 64 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who have a sustained virologic response (SVR; i.e., HCV RNA concentration below the lower limit of quantitation [<LLOQ; <25 IU/mL]) at 4 weeks after the last planned dose of treatment (SVR4) |  | Up to 20 Weeks | 
| The proportion of subjects who have an SVR at 12 weeks after the last planned dose of treatment (SVR12) |  | Up to 28 weeks | 
| The proportion of subjects who have an SVR at 44 weeks after the last planned dose of treatment (SVR24) |  | Up to 40 weeks | 
| The proportion of subjects who have virologic relapse |  | Up to 64 weeks | 
| The proportion of subjects who have virologic breakthrough |  | Up to 16 weeks | 
| The amino acid sequence of the nonstructural NS5A and NS5B proteins in subjects who have treatment failure |  | Up to 64 weeks | 
| The proportion of subjects who achieve SVR12 by HCV genotype 1 subtype (1a versus non-1a) |  | Up to 28 weeks | 
| The proportion of subjects who achieve SVR12 by IL-28B genotype (CC versus non-CC) |  | Up to 28 weeks |