UNITY 3: A Japanese Phase 3 Study of a Daclatasvir/Asunaprevir/BMS-791325 in Subjects With Genotype 1 Chronic Hepatitis C

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that the proportion of treatment-naive non-cirrhotic subjects with Genotype (GT)-1b treated with Daclatasvir (DCV)/Asunaprevir (ASV)/BMS-791325 who achieve Sustained Virologic response (SVR12), defined as Hepatitis C virus (HCV) RNA < LOQ target detected or target not detected (LOQ TD/TND) at follow-up Week 12, is significantly higher than SVR12 of current Standard of Care (SOC).

Detailed Description
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Limit of Quantitation (LOQ) Ribonucleic acid (RNA) End of Treatment (EOT) Triple Direct Acting Antivirals (3DAA)

Official Title
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A Japanese Phase 3 Study of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination (FDC) in Treatment-Naive and IFN Experienced Subjects With Genotype 1 Chronic Hepatitis C

Conditions
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Hepatitis C Virus Infection

Intervention / Treatment
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* Drug: Daclatasvir
* Drug: Asunaprevir
* Drug: DCV 3DAA
* Other: Placebo for DCV 3DAA
* Other: Placebo for Daclatasvir
* Other: Placebo for 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: Males and females, ≥ 20 years of age Subjects chronically infected with HCV GT-1 HCV RNA viral load of ≥ 100,000 IU/mL Exclusion Criteria: Hepatocellular carcinoma Co-infection with Hepatitis B virus (HBV) or Human immunodeficiency virus (HIV) Severe or uncontrollable complication

Ages Eligible for Study
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Minimum Age: 20 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: Arm 1: DCV 3DAA + Placebo for DCV/Placebo for ASV<br>DCV 3DAA tablet orally twice daily for 12 weeks + Placebo for DCV tablet orally once daily and Placebo for ASV capsule orally twice daily for 24 weeks (Double blind) | Drug: DCV 3DAA<br> <br> * Other names: Daclatasvir 30 mg /Asunaprevir 200 mg /BMS-791325 75 mg fixed dose combination;Other: Placebo for Daclatasvir<br> <br> Other: Placebo for Asunaprevir<br> <br> |
| Active Comparator: Arm 2: DCV/ASV + Placebo for DCV 3DAA<br>Daclatasvir 60 mg tablet orally once daily and Asunaprevir 100 mg capsule orally twice daily for 24 weeks + Placebo for DCV 3DAA tablet orally twice daily for 12 weeks (Double blind) | Drug: Daclatasvir<br> <br> Drug: Asunaprevir<br> <br> Other: Placebo for DCV 3DAA<br> <br> |
| Experimental: DCV 3DAA<br>DCV 3DAA (open label) Tablet orally twice daily for 12 weeks | Drug: DCV 3DAA<br> <br> * Other names: Daclatasvir 30 mg /Asunaprevir 200 mg /BMS-791325 75 mg fixed dose combination;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects who achieve SVR12 in treatment-naive non-cirrhotic subjects treated with DCV/ASV/BMS-791325, defined as HCV RNA < LOQ target detected or target not detected (LOQ TD/TND) at post-treatment follow-up Week 12 |  | After 12 weeks of the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of treatment-naive subjects who achieve SVR12 with DCV/ASV/BMS-791325 or DCV/ASV |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| The proportion of Interferon (IFN) experienced subjects who achieve SVR12 with DCV/ASV/BMS-791325 |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| The proportion of subjects who achieve HCV RNA < LOQ TD/TND at each of the following Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT; post-treatment Weeks 4 (SVR4), 8 (SVR8) and 24 (SVR24) |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| The proportion of subjects who achieve HCV RNA < LOQ TND at each of the following Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT; post-treatment Weeks 4, 8, 12 and 24 |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| On-treatment safety as measured by the frequency of Serious Adverse Event (SAEs), discontinuations due to Adverse Event (AEs), and selected Grade 3 - 4 laboratory abnormalities | based on the US National Institutes of Health Division of AIDs (DAIDS) criteria | Approximately 48 weeks | 
| The proportion of subjects with anemia defined as Hb < 10 g/dL on-treatment who had Hb ≥ 10 g/dL at baseline |  | Approximately 48 weeks | 
| The proportion of subjects in each cohort who achieve SVR12 associated with HCV genotype subtype 1a vs 1b |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| The proportion of subjects in each cohort who achieve SVR12 associated with IL28B Single Nucleotide Polymorphisms (SNP) status |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| The proportion of cirrhotic and non-cirrhotic subjects who achieve SVR12 |  | Weeks: 1, 2, 4, 6, 8, 12, 16, 20 and 24; EOT (week 12 or 24); post-treatment Weeks 4, 8, 12 and 24 | 
| On-treatment safety of non-cirrhotic vs cirrhotic subjects, as measured by the frequency of SAEs, discontinuations due to AEs, and selected Grade 3 - 4 laboratory abnormalities on DAIDS criteria |  | Approximately 48 weeks |