A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a regimen consisting of daclatasvir and asunaprevir is effective in treatment-naive patients with chronic hepatitis genotype 1b infection.

Official Title
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A Phase 3 Evaluation of Daclatasvir and Asunaprevir in Treatment-naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Asunaprevir


Participation Criteria
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Eligibility Criteria
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For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com Inclusion Criteria: Patients chronically infected with HCV Genotype 1b No previous exposure to any interferon formulation, Ribavirin (RBV), and HCV direct acting antiviral agent HCV RNA viral load ≥ 10,000 IU/mL at screening Seronegative for HIV and HBsAg BMI of 18-35 kg/m2, inclusive Patients with compensated cirrhosis are permitted Exclusion Criteria: Infection with HCV other than genotype (GT) -1b Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy Evidence of a medical condition contributing to chronic liver disease other than HCV Diagnosed or suspected hepatocellular carcinoma or other malignancies Uncontrolled diabetes or hypertension History of moderate to severe depression. Well-controlled mild depression is allowed Confirmed alanine aminotransferase (ALT) ≥ 5x Upper Limit of Normal (ULN) Confirmed platelet count < 50,000 cells/mm3 Confirmed hemoglobin < 8.5 g/dL

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: Active dual arm<br>Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 24 week and follow up to week 48 | Drug: Daclatasvir<br>* Daclatasvir tablet 60mg<br>Drug: Asunaprevir<br>* Asunaprevir soft capsule 100 mg<br>|
| Placebo Comparator: Placebo arm<br>Daclatasvir placebo in tablet form QD and Asunaprevir placebo in soft capsule form BID from day 1 to 12 week Daclatasvir in tablet form at the dose of 60 mg QD and Asunaprevir in soft capsule form at the dose of 100 mg BID from 12 to 36 week and follow up to week 60 | Drug: Daclatasvir<br>* Daclatasvir tablet 60mg<br>Drug: Asunaprevir<br>* Asunaprevir soft capsule 100 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects randomized to Active Dual therapy with Sustained Virologic Response (SVR12) | HCV RNA < Lower limit of quantitation (LLOQ) target detected (TD) or target not detected (TND) at follow-up Week 12 | Post-treatment Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with anemia on active Dual therapy |  | Post-treatment Week 12 | 
| Proportion of subjects with neutropenia on active Dual therapy |  | Post-treatment Week 12 | 
| Proportion of subjects with thrombocytopenia on active Dual therapy |  | Post-treatment Week 12 | 
| On treatment safety, as measured by frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Post-treatment week 12 | 
| Differences in rates of selected Grade 3-4 laboratory abnormalities for hematology between treatments (DCV + Asunaprevir (ASV) vs PBO) |  | first 12 weeks on treatment | 
| Differences in rates of selected Grade 3-4 laboratory abnormalities for liver function between treatments (DCV + Asunaprevir (ASV) vs PBO) |  | first 12 weeks on treatment | 
| Proportion of subjects with SVR12 by the rs12979860 single nucleotide polymorphism (SNP) in the interleukin (IL) -28B gene for each cohort |  | Post-treatment visit week 12 | 
| Proportion of subjects with hepatitis C virus (HCV) RNA < LLOQ-TD/TND in each arm at various intervals after the initiation of active Dual therapy |  | post-treatment visit Week 24 | 
| Proportion of subjects who achieve HCV RNA < LLOQ-TND at each arm at various intervals after the initiation of active Dual therapy |  | post-treatment visit Week 24 | 
| Proportion of treated subjects with SVR12 for subjects randomized to placebo |  | Post-treatment visit week 12 |