Efficacy and Safety Evaluation of a Treatment Consisting of Peg Interferon Alfa + Ribavirin + Daclatasvir in HCV Genotype 1 and 4 Treatment naïve Patients

Study Overview
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Brief Summary
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The purpose of this study is to determine whether 24 week treatment with the Daclatasvir (DCV) in combination with Pegylated-interferon alfa 2a (pegIFNα-2a) and Ribavirin (RBV) is safe and demonstrates rate of Sustained Virologic Response at follow up week 24 (SVR24) (defined as undetectable HCV RNA at post-treatment Week 24) that are non-inferior to 48 weeks of the dual combination therapy of pegIFNα-2a/RBV in a majority of study subjects

Official Title
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A Phase 3 Randomized, Double Blind, Multi-National Evaluation of Daclatasvir in Combination With Peg Interferon Alfa-2a and Ribavirin in Treatment-Naive Subjects With Chronic Hepatitis C Genotypes 1 and 4

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Peginterferon alfa 2a
* Drug: Ribavirin
* Drug: Placebo matching Daclatasvir
* Drug: Daclatasvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients chronically infected with Hepatitis C virus (HCV) GT 1 or 4 HCV RNA viral load ≥ 10,000 IU/mL Naïve to prior treatment with any interferon formulation, Ribavirin (RBV) or HCV direct antiviral agent Patients with compensated cirrhosis are permitted Exclusion Criteria: Infected with HCV other than GT 1 or 4 Evidence of decompensated liver disease Documented or suspected Hepatocellular carcinoma (HCC) as evidenced by previously obtained imaging studies or liver biopsy Evidence of a medical condition contributing to chronic liver disease other than HCV History of chronic Hepatitis B virus (HBV) or Human immunodeficiency virus (HIV) Current or know history of cancer (except in situ carcinoma of cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to enrollment Laboratory values: Hemoglobin < 12 g/dL (females) or < 13 g/dL (males) Platelets < 90 x 1000000000 cells/L Absolute neutrophil count (ANC) < 1.5 × 1000000000 cells/L Total bilirubin ≥ 34 µmol/L (unless due to Gilbert's disease)

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: pegIFNα 2a + Ribavirin + Placebo<br>pegIFNα 2a 180 µg, Solution for injection, Subcutaneous, Once weekly, 48 weeks Ribavirin 200 mg Tablets, by mouth, 400-600mg AM, 600 mg PM, 48 weeks Placebo 0 mg Tablets, by mouth, Once daily, 24 weeks | Drug: Peginterferon alfa 2a<br> <br> * Other names: Pegasys®;Drug: Ribavirin<br> <br> * Other names: Wei Lining (China);Drug: Placebo matching Daclatasvir<br> <br> |
| Experimental: pegIFNα 2a + Ribavirin + Daclatasvir<br>pegIFNα 2a 180 µg, Solution for injection, Subcutaneous, Once weekly, 24 or 48 weeks depending on response Ribavirin 1000-1200 mg Tablets, by mouth, 400-600mg AM, 600 mg PM, 24 or 48 weeks depending on response Daclatasvir 60 mg Tablets, by mouth, Once daily, 24 weeks | Drug: Peginterferon alfa 2a<br> <br> * Other names: Pegasys®;Drug: Ribavirin<br> <br> * Other names: Wei Lining (China);Drug: Daclatasvir<br> <br> * Other names: BMS-790052-05;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Genotype 1 subjects with SVR24, defined as HCV RNA < Limit of quantification (LOQ) at follow-up Week 24 for each cohort |  | Week 24 post treatment follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Genotype (GT) 4 subjects with SVR24 |  | Week 24 post treatment follow up visit | 
| Proportion of GT 1 & 4 subjects who achieve HCV RNA < LOQ or undetectable |  | Week 24 post treatment follow up visit and Week 48 post treatment follow up visit for subjects who achieve Virologic response [VR] (4&12) | 
| Frequency of Serious Adverse Events (SAEs)/discontinuations due to Adverse Events (AEs) |  | Up to 48 weeks plus 30 days | 
| Discontinuations due to Adverse Events (AEs) |  | Up to 48 weeks plus 7 days | 
| Proportion of subjects with Sustained Virologic Response at follow up week 12 (SVR12) or SVR24 by rs12979860 Single nucleotide polymorphism (SNP) in the IL28B gene |  | Up to 72 weeks |