A Phase 3 Study of a Daclatasvir/Asunaprevir/BMS-791325 Fixed Dose Combination (FDC) in Subjects With Chronic Hepatitis C Genotype 1

Study Overview
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Brief Summary
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To demonstrate the effectiveness of Daclatasvir (DCV) 3 Direct Acting Antivirals (DAA) fixed dose combination in Genotype 1 Chronic Hepatitis C subjects.

Detailed Description
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US National Institutes of Health Division of AIDs (DAIDS)

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

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: DCV/ASV/BMS-791325


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: Subject chronically infected with HCV genotype 1 (GT-1) Subject without cirrhosis or with compensated cirrhosis (Child Pugh Class A) HCV RNA ≥ 10,000 IU/mL at screening Treatment-naïve subject with no previous exposure to an interferon formulation (ie, IFNα, pegIFNα), Ribavirin (RBV), or HCV DAA (protease, polymerase inhibitor, etc.) Interferon (IFN) experienced subject who have received previous treatment with IFNα, with or without RBV Exclusion Criteria: Liver or any other transplant (including hematopoietic stem cell transplants) other than cornea and hair; Current or known history of cancer (except in situ carcinoma of the cervix or adequately treated basal or squamous cell carcinoma of the skin) within 5 years prior to screening; Documented or suspected hepatocellular carcinoma (HCC), as evidenced by previously obtained imaging studies or liver biopsy (or on a screening imaging study/liver biopsy if this was performed); Evidence of decompensated liver disease including, but not limited to, radiologic criteria, a history or presence of ascites, bleeding varices, or hepatic encephalopathy
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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1 : DCV/ASV/BMS-791325<br>DCV 30 mg (as the free base) / Asunaprevir (ASV) 200 mg / BMS-791325 75 mg FDC tablet orally twice daily for 12 weeks | Drug: DCV/ASV/BMS-791325<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 (SVR12) in the Naive Cohort | Percentage of Participants with SVR12 in the naive cohort, defined as HCV RNA < LLOQ target detected (TD) or target not detected (TND) (LOQ TD/TND) at post-treatment follow-up Week 12. | Post treatment Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With SVR12 in the Interferon Alfa (IFN-a) Experienced Cohort | Percentage of treated participants with SVR12 in the IFNα experienced cohort, defined as HCV RNA < LLOQ target detected or target not detected (LLOQ TD/TND). | Post treatment Week 12 | 
| Percentage of Participants Who Achieved HCV RNA < LLOQ TD/TND | Percentage of Participants with hepatitis C virus(HCV) ribonucleic acid (RNA) < lower limit of quantitation (LLOQ), target detected (TD) or target not detected (TND) were presented at treatment Weeks 1, 2, 4, 6, 8, 12, EOT, and follow-up Weeks 4 (SVR4), 8 (SVR8), and 24 (SVR24). | On-treatment Weeks: 1, 2, 4, 6, 8, and 12; post treatment Weeks 4 (SVR4), 8 (SVR8), 24 (SVR24) and EOT (end of treatment) | 
| Percentage of Participants Who Achieved HCV RNA < LLOQ TND | Percentage of treated participants with HCV RNA < LLOQ, TND (target not detected) were presented at treatment Weeks 1, 2, 4, 6, 8, 12, at both Weeks 4 and 12, EOT, and follow-up Weeks 4, 8, 12 and 24. | On-treatment Weeks: 1, 2, 4, 6, 8, and 12 and post treatment weeks 4, 8, 12, 24 and EOT (end of treatment) | 
| Number of Participants With Deaths, Serious Adverse Events (SAEs) and AEs Leading to Discontinuation From Treatment | SAE is defined as any untoward medical occurrence that, at any dose results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/ birth defect. | Up to post treatment week 4 | 
| Percentage of Participants With Anemia Defined as Hb < 10 g/dL On-treatment Who Had Hb >=10 g/dL at Baseline | Anemia was defined as hemoglobin < 10 g/dL on-treatment for subjects who had hemoglobin >= 10 g/dL at baseline. | Up to post treatment week 4 | 
| Percentage of Participants Who Achieved SVR12 Associated With Hepatitis C Virus (HCV) Genotype Subtype 1a vs 1b | Percentage of subjects in each cohort who achieved SVR12 associated with HCV genotype subtype 1a vs 1b were reported. | Post treatment week 12 | 
| Proportion of Participants Who Achieved SVR12 Associated With IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) Status (CC Genotype or Non CC Genotype) | Proportion of Participants who Achieved SVR12 Associated with IL28B rs12979860 Single Nucleotide Polymorphisms (SNP) status (CC genotype or non CC genotype) were reported. | Post treatment Week 12 | 
| Proportion of Cirrhotic and Non Cirrhotic Participants Who Achieved SVR12 | Proportion of Cirrhotic and Non Cirrhotic Participants who Achieved SVR12 were reported. | Post treatment Week 12 | 
| Number of Participants With Selected Grade 3/4 Laboratory Abnormalities | Rates of selected Grade 3 - 4 laboratory abnormalities on treatment in each cohort was estimated | Post treatment week 4 | 
| Number of Participants With/Without Cirrhosis as Measured by SAEs and Discontinuations Due to AEs | Subgroup analysis of on-treatment safety with non-cirrhosis vs cirrhosis, as measured by the frequency of SAEs, discontinuations due to AEs was conducted. | Up to post treatment week 4 | 
| Number of Participants With/Without Cirrhosis as Measured by Selected Grade 3-4 Laboratory Abnormalities | Subgroup analysis of on-treatment safety with non-cirrhosis vs cirrhosis, as measured by the selected Grade 3 - 4 laboratory abnormalities (including hematologic and liver function, based on DAIDS criteria) was conducted. | Up to post treatment week 4 |