A Study of BMS-824393 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype I

Study Overview
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Brief Summary
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Based on 12-week on-treatment data, at least 1 dose of BMS-824393 can be identified which is safe, well tolerated, and has sufficient antiviral activity to progress to late stage clinical trials when combined with pegIFNα/RBV for treatment of chronically infected hepatitis C virus genotype 1 treatment-naive subjects.

Official Title
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A Randomized, Placebo-controlled, Phase 2a Study of BMS-824393 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment Naive Subjects With Chronic Hepatitis C Virus Genotype I

Conditions
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Chronic Hepatitis C Virus Genotype 1

Intervention / Treatment
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* Drug: BMS-824393
* Drug: BMS-824393
* Drug: BMS-824393
* Drug: Placebo
* Drug: Peginterferon Alpha-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Treatment-naive subjects with genotype 1 chronic HCV HCV RNA ≥ 100,000 IU/mL at screening Seronegative for HIV and HBsAg Liver biopsy within prior 2 years demonstrating no cirrhosis Exclusion Criteria: Any evidence of liver disease other than hepatitis C Diagnosed or suspected hepatocellular carcinoma Laboratory values: neutrophil count < 1500 cells/μL, platelet count < 90,000/μL; Hemoglobin ≤ 12 g/dL (120g/L) for women and ≤ 13 g/dL (130 g/L) for men Cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: BMS-824393 (10mg)<br>Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12 | Drug: BMS-824393<br>* Capsule, Oral, 10 mg, once daily<br>Drug: Peginterferon Alpha-2a<br>* Syringe, subcutaneous 180 mcg/0.5 mL, weekly<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily<br>* Other names: Copegus;|
| Experimental: BMS-824393 (30 mg)<br>Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12 | Drug: BMS-824393<br>* Capsule, Oral, 30 mg, once daily<br>Drug: Peginterferon Alpha-2a<br>* Syringe, subcutaneous 180 mcg/0.5 mL, weekly<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily<br>* Other names: Copegus;|
| Experimental: BMS-824393 (100 mg)<br>Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12 | Drug: BMS-824393<br>* Capsule, Oral, 100 mg, once daily<br>Drug: Peginterferon Alpha-2a<br>* Syringe, subcutaneous 180 mcg/0.5 mL, weekly<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily<br>* Other names: Copegus;|
| Placebo Comparator: Placebo<br>Plus Peginterferon Alfa-2a and Ribavirin Day 1 - Week 12 | Drug: Placebo<br>* Capsule, Oral, 0 mg, once daily<br>Drug: Peginterferon Alpha-2a<br>* Syringe, subcutaneous 180 mcg/0.5 mL, weekly<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily<br>* Other names: Copegus;|
| Other: Peginterferon alfa-2a plus Ribavirin<br>Weeks 13 - 48 | Drug: Peginterferon Alpha-2a<br>* Syringe, subcutaneous 180 mcg/0.5 mL, weekly<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 400 or 600 mg based on weight (am) and 600 mg (pm), twice daily<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Week 4 | 
| Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Week 12 | 
| Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Week 24 | 
| Safety as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Week 48 | 
| Antiviral activity as determined by the proportion of subjects with extended rapid virologic response (eRVR) defined as undetectable HCV RNA |  | Week 4 | 
| Antiviral activity as determined by the proportion of subjects with extended rapid virologic response (eRVR) defined as undetectable HCV RNA |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with rapid virologic response (RVR), defined as undetectable RNA |  | Week 4 | 
| Proportion of subjects with complete early virologic response (cEVR), defined as undetectable HCV RNA |  | Week 12 | 
| Proportion of subjects with a sustained virologic response (SVR), defined as HCV RNA undetectable |  | Week 12 (SVR12) | 
| Proportion of subjects with a sustained virologic response (SVR), defined as HCV RNA undetectable |  | Week 24 (SVR24) | 
| Resistant variants associated with virologic failure |  | Week 4 | 
| Resistant variants associated with virologic failure |  | Week 12 | 
| Resistant variants associated with virologic failure |  | Follow up Week 12 | 
| Resistant variants associated with virologic failure |  | Week 24 |