Phase III Hallmark DUAL: ASV+DCV (Nulls/Partials, Intolerants/Ineligibles. Naives)

Study Overview
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Brief Summary
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The purpose of this study is to estimate efficacy, as determined by the proportion of subjects with Sustained virologic response at post-treatment Week 12 (SVR12), defined as Hepatitis C virus (HCV) Ribonucleic acid (RNA) < Limit of quantitation (LOQ) at post-treatment Week 12, for subjects who are prior null or partial responders to P/R or who are treatment-naive.

Detailed Description
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Allocation: Treatment naive cohort: Randomized Controlled Trial, Null/partial responder and intolerant/ineligible cohorts: N/A (Single arm study) Masking: Treatment naive cohort: Double Blind, Null/partial responder and intolerant/ineligible cohorts: Open Intervention Model: Treatment naive cohort: Parallel, Null/partial responder and intolerant/ineligible cohorts: Single group

Official Title
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A Phase 3 Study With Asunaprevir and Daclatasvir (DUAL) for Null or Partial Responders to Peginterferon Alfa and Ribavirin (P/R), Intolerant or Ineligible to P/R Subjects and Treatment-Naive Subjects With Chronic Hepatitis C Genotype 1b Infection

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: Asunaprevir (ASV)
* Drug: Daclatasvir (DCV)
* Drug: Pegylated-interferon alfa 2a (PegIFN)
* Drug: Ribavirin (RBV)


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, ≥ 18 years of age HCV Genotype 1b who previously failed treatment with peginterferon alfa and ribavirin, classified as previous null or partial responders based on previous therapy, OR intolerant or ineligible to P/R due to neutropenia, anemia, depression or thrombocytopenia with fibrosis/cirrhosis, OR treatment naive HCV RNA ≥ 10,000 IU/mL Seronegative for Human immunodeficiency virus (HIV) and Hepatitis B surface antigen (HBsAg) Subjects with compensated cirrhosis are permitted (compensated cirrhotics are capped at approximately 25% of treated population) Exclusion Criteria: Prior treatment of HCV with HCV direct acting antiviral (DAA) Evidence of a medical condition contributing to chronic liver disease other than HCV Evidence of decompensated liver disease including, but not limited to, a history or presence of ascites, bleeding varices, or hepatic encephalopathy Diagnosed or suspected hepatocellular carcinoma or other malignancies Uncontrolled diabetes or hypertension

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: Arm 1: Null or Partial Responder to P/R (ASV + DCV)<br>Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks | Drug: Asunaprevir (ASV)<br> <br> * Other names: BMS-650032;Drug: Daclatasvir (DCV)<br> <br> * Other names: BMS-790052;|
| Experimental: Arm 2: Intolerant to or Ineligible for P/R (ASV + DCV)<br>Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 Weeks | Drug: Asunaprevir (ASV)<br> <br> * Other names: BMS-650032;Drug: Daclatasvir (DCV)<br> <br> * Other names: BMS-790052;|
| Experimental: Arm 3: Treatment naive (ASV + DCV)<br>[Subjects will receive ASV + DCV for 24 weeks] followed by ASV + DCV for 24 weeks in protocol AI444026] Subjects meeting prespecified rescue criteria in the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg/1200 mg (total daily dose) tablet by mouth for 24 or 48 weeks | Drug: Asunaprevir (ASV)<br> <br> * Other names: BMS-650032;Drug: Daclatasvir (DCV)<br> <br> * Other names: BMS-790052;Drug: Pegylated-interferon alfa 2a (PegIFN)<br> <br> * Other names: Pegasys;Drug: Ribavirin (RBV)<br> <br> * Other names: Copegus;|
| Experimental: Arm 4: Null or Partial Responder to P/R (ASV + DCV) 24/48 week<br>Subjects meeting prespecified rescue criteria in the null or partial responder cohort or active arm of the treatment naive cohort may have therapeutic rescue instituted with QUAD regimen (QUAD= ASV + DCV + P/R) Asunaprevir 100 mg Capsules by mouth, Twice daily for 24 or 48 Weeks Daclatasvir 60 mg Tablet by mouth, Once daily for 24 or 48 Weeks Pegylated-interferon alfa 2a (PegIFN) 180 mcg/0.5 mL injection subcutaneously (SC), once weekly for 24 or 48 weeks Ribavirin 1000 mg / 1200 mg (total daily dose) Tablet by mouth, for 24 or 48 weeks | Drug: Asunaprevir (ASV)<br> <br> * Other names: BMS-650032;Drug: Daclatasvir (DCV)<br> <br> * Other names: BMS-790052;Drug: Pegylated-interferon alfa 2a (PegIFN)<br> <br> * Other names: Pegasys;Drug: Ribavirin (RBV)<br> <br> * Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post treatment Week 12, for subjects who are prior null or partial responders to P/R or are treatment-naive |  | At 12 weeks post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of treated subjects with SVR12, defined as HCV RNA < LOQ at post-treatment Week 12, for subjects who are intolerant or ineligible to P/R |  | Post-treatment Week 12 | 
| On treatment safety, as measured by frequency of Serious Adverse Events (SAEs) and discontinuations due to Adverse Events (AEs) |  | End of Treatment (up to 48 weeks) plus 7 days | 
| Differences in rates of selected grade 3-4 laboratory abnormalities during the first 12 weeks between treatments (ASV + DCV vs PBO) for naive subjects |  | Up to first 12 weeks | 
| Proportion of genotype 1b subjects with SVR12 (HCV RNA < LOQ at post treatment Week 12) by the rs12979860 single nucleotide polymorphisms (SNP) in the IL28B gene for each cohort |  | Post-treatment Week 12 | 
| Proportion of genotype 1b subjects with HCV RNA undetectable | eRVR = Extended rapid virologic response, EOT = End of treatment | At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [eRVR]; EOT (up to 24 weeks), post-treatment Week 12, or post-treatment Week 24 for each cohort | 
| Proportion of genotypes 1b subjects with HCV RNA < LOQ |  | At weeks 1, 2, 4, 6, 8 and 12; at both Weeks 4 and 12 [VR(4&12)]; EOT (up to 24 weeks), post-treatment Week 24 (SVR24) for each cohort | 
| Proportion of subjects with anemia |  | At 12 weeks post-treatment | 
| Proportion of subjects with rash |  | At 12 weeks post-treatment |