Study of BMS-650032 With Peginterferon Alfa-2a Plus Ribavirin

Study Overview
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Brief Summary
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The purpose of this study is to identify one or more doses of BMS-650032 that, when used in combination with pegylated-interferon alpha and ribavirin are safe and demonstrate sufficient activity against hepatitis C virus (Genotypes 1 and 4).

Official Title
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A Phase 2a/2b Study of BMS-650032 in Combination With Peginterferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naive Subjects With Genotypes 1 and 4 Chronic Hepatitis C Infection

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: BMS-650032
* Drug: BMS-650032
* Drug: Placebo
* Drug: Placebo
* Drug: Placebo
* Drug: Peginterferon Alfa-2a
* Drug: Peginterferon Alfa-2a
* Drug: Ribavirin
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects chronically infected with HCV genotype 1 (Phase 2a and Phase 2b) Subjects chronically infected with HCV genotype 4 (Phase 2b only) HCV RNA viral load of ≥ 10*5* IU/mL at screening BMI of 18 - 35 kg/m² at screening Exclusion Criteria: Cirrhosis (Phase 2a only) Decompensated cirrhosis (Phase 2b) Co-infection with HBV or HIV Hepatocellular carcinoma Prior treatment with anti-HCV drugs

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 2a: Arm 1<br> | Drug: BMS-650032<br>* Tablets, Oral, 200 mg, Twice Daily, 48 weeks<br>Drug: Peginterferon Alfa-2a<br>* Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks<br>* Other names: Copegus;|
| Placebo Comparator: Phase 2a: Arm 2<br> | Drug: Placebo<br>* Tablets, Oral, 0 mg, twice daily, 48 weeks<br>* Other names: Pegasys;Drug: Peginterferon Alfa-2a<br>* Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks<br>* Other names: Copegus;|
| Experimental: Phase 2b: Arm 1<br> | Drug: BMS-650032<br>* Tablets, Oral, 200 mg, Twice Daily, 12 or 24 weeks, depending on response<br>Drug: Placebo<br>* Tablets, Oral, 0 mg, twice daily, 0 or 12 weeks (depending on response) beginning at Week 12<br>Drug: Peginterferon Alfa-2a<br>* Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 24 or 48 weeks, depending on response<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 24 or 48 weeks depending on response<br>* Other names: Pegasys;|
| Placebo Comparator: Phase 2b: Arm 2<br> | Drug: Placebo<br>* Tablets, Oral, 0 mg, twice daily 24 weeks<br>Drug: Peginterferon Alfa-2a<br>* Syringe, Subcutaneous injection, 180 mcg / 0.5 mL, Weekly, 48 weeks<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablet, Oral, 500 or 600 mg based on weight, Twice Daily, 48 weeks<br>* Other names: Copegus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2a and Phase 2b: Safety, as measured by the frequency of SAEs and discontinuations due to AEs |  | 12 weeks after first dose | 
| Antiviral activity as determined by proportion of HCV genotype 1 subjects with extended rapid virologic response (eRVR), defined as undetectable HCV RNA |  | Week 4 | 
| Antiviral activity as determined by proportion of HCV genotype 1 subjects with extended rapid virologic response (eRVR), defined as undetectable HCV RNA |  | Week 12 | 
| Phase 2b only: Antiviral activity, as determined by the proportion of HCV genotype 1 subjects with 24-week sustained virologic response (SVR24), defined as undetectable HCV RNA |  | at follow-up Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of HCV genotype 1 subjects with rapid virologic response (RVR), defined as undetectable HCV RNA at Week 4 |  | Week 4 | 
| Proportion of HCV genotype 1 subjects with complete early rapid virologic response (eEVR), defined as undetectable HCV RNA at Week 12 (Stage 2 only) |  | at Week 12 (Stage 2 only) | 
| Proportion of HCV genotype 1 subjects with early virologic response (EVR) defined as ≥2 log10 decrease in HCV RNA from baseline at Week 12 (Stage 1 only) |  | Week 12 (Stage 1 only) | 
| Proportion of HCV genotype 1 subjects with 12-week sustained virologic response (SVR12), defined as undetectable HCV RNA at follow-up Week 12 |  | follow-up Week 12 | 
| Proportion of HCV genotype 1 subjects with 24-week sustained virologic response (SVR24) defined as undetectable HCV RNA at follow-up Week 24 (Stage 1 only) |  | follow-up Week 24 (Stage 1 only) | 
| Resistant variants associated with virologic failure |  | 48 weeks after last dose |