UNITY 2: A Study of an Investigational Treatment Regimen of DCV+ASV+BMS-791325 in a Fixed Dose Combination (the DCV 3DAA (Direct Acting Antiviral) Regimen) With or Without RBV for 12 Weeks for the Treatment of Chronic Hepatitis C Virus(HCV)Genotype 1 Infection in Subjects With Compensated Cirrhosis

Study Overview
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Brief Summary
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To demonstrate the effectiveness of DCV 3DAA fixed dose combination with or without Ribavirin in treatment naive cirrhotic subjects.

Detailed Description
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Masking is Double blind for RBV: two or more parties are unaware of the intervention assignment.

Official Title
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A Phase 3 Evaluation of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination in Subjects With Genotype 1 Chronic Hepatitis C and Compensated Cirrhosis

Conditions
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Hepatitis C

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Asunaprevir
* Drug: BMS-791325
* Drug: Ribavirin
* Drug: Placebo matching Ribavirin


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: Subjects chronically infected with HCV genotype 1 Subjects with compensated cirrhosis HCV RNA ≥ 10,000 IU/mL at screening Treatment-naïve subjects with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), Ribavirin (RBV), or HCV Direct Acting Antivirals (DAA) (protease, polymerase inhibitor, etc.) Treatment-experienced subjects are eligible including exposure to anti-HCV agents of a mechanistic class other than those contained in the Daclatasvir (DCV) / Asunaprevir (ASV) /BMS-791325 triple regimen is permitted. Examples of permitted agents include, but are not limited to nucleoside/nucleotide inhibitors of nonstructural protein 5B (NS5B) polymerase, inhibitors of cyclophilin, or inhibitors of microRNA. Exclusion Criteria: Subjects without cirrhosis Liver or any other organ transplant Current or known history of cancer within 5 years prior to screening Documented or suspected hepatocellular carcinoma(HCC) Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A1: DCV/ASV/BMS-791325+Placebo matching RBV (naive)<br>Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0mg tablet orally twice a day for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: BMS-791325<br> <br> Drug: Placebo matching Ribavirin<br> <br> |
| Experimental: A2: DCV/ASV/BMS-791325 + RBV (naive)<br>Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200mg tablet orally twice a day for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: BMS-791325<br> <br> Drug: Ribavirin<br> <br> * Other names: Ribasphere®;|
| Experimental: A3: DCV/ASV/BMS-791325+Placebo matching RBV (experienced)<br>Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Placebo matching Ribavirin 0 mg tablet orally twice a day for 12 weeks | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: BMS-791325<br> <br> Drug: Placebo matching Ribavirin<br> <br> |
| Experimental: A4: DCV/ASV/BMS-791325 + RBV (experienced)<br>Triple fixed dose combination (Daclatasvir 30 mg, Asunaprevir 200 mg, BMS-791325 75 mg) tablet orally twice a day for 12 weeks Ribavirin 200 mg tablet orally twice a day for 12 weeks, Weight based dosing: If < 75 kg, 1000 mg per day (two 200 mg tablets in AM and three 200 mg tablets in PM); if ≥ 75 kg, 1200 mg per day (three 200 mg tablets in AM and three 200 mg tablets in PM), AM=in the morning, PM=in the evening | Drug: Daclatasvir<br> <br> * Other names: BMS-790052;Drug: Asunaprevir<br> <br> * Other names: BMS-650032;Drug: BMS-791325<br> <br> Drug: Ribavirin<br> <br> * Other names: Ribasphere®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects in each of the naive arms with sustained virologic response (SVR12) | SVR12 is defined as Hepatitis C virus ribonucleic acid (HCV RNA) < Limit of Quantification (LOQ) target detected or target not detected (LOQ TD/TND) | Post treatment 12 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects in each of the experienced arms with SVR12 |  | Post treatment 12 Week | 
| Proportion of subjects in each arm who achieve HCV RNA < LOQ TD/TND |  | Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24) | 
| Proportion of subjects in each arm who achieve HCV RNA < LOQ TND |  | Weeks: 1, 2, 4, 6, 8, and 12; Post treatment Weeks 4 (SVR4), 8 (SVR8), 12 (SVR12) and 24 (SVR24) | 
| Safety as measured by frequency of Serious Adverse Events(SAEs)and discontinuations due to Adverse Events(AEs) |  | Up to end of treatment (week 12) + 7 days | 
| Proportion of subjects with anemia defined as Hg < 10 g/dL on-treatment and Hg ≥ 10 g/dL at baseline in each arm within each cohort |  | Up to end of treatment (week 12) + 7 days | 
| Differences in rates of selected Grade 3 - 4 laboratory test result abnormalities |  | Up to end of treatment (week 12) + 7 days | 
| Proportion of subjects achieving SVR12 associated with HCV geno subtype 1a vs 1b |  | Post treatment 12 Week | 
| Proportion of subjects in each arm achieving SVR12 associated with IL28B rs12979860 single nucleotide polymorphism(SNP) status (CC genotype or non-CC genotype) |  | Post treatment 12 Week |