Ph IIA Study (SOC +/- NS5B)

Study Overview
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Brief Summary
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At least 1 dose of BMS-791325 can be identified which is safe, well tolerated, and efficacious when combined with peg-interferon alfa-2a (pegIFNα-2a)/ribavirin (RBV) for the treatment of treatment-naïve, chronically-infected hepatitis C virus (HCV) genotype 1 subjects

Official Title
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A Phase 2A Study of BMS-791325 in Combination With Peg Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Treatment-Naïve Subjects With Chronic Hepatitis C Virus Genotype 1 Infection

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: BMS-791325
* Drug: BMS-791325
* Drug: Placebo
* Drug: Peg-interferon alfa-2a
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects chronically infected with HCV genotype 1 as documented by: positive for anti-HCV antibody, HCV RNA, or a positive HCV genotype test at least 6 months prior to Screening, and positive for HCV RNA and anti-HCV antibody at Screening HCV RNA ≥ 10*5* IU/mL at Screening Less than 4 weeks total prior therapy with an IFN formulation (ie, IFNα, pegIFNα-2a), or RBV and no exposure to IFN or RBV within 24 weeks of Randomization Results of a biopsy obtained ≤ 24 months prior to Randomization showing no evidence of cirrhosis Body Mass Index (BMI) of 18 to 35 kg/m², inclusive. BMI = weight (kg)/ [height (m)]² at Screening Exclusion Criteria: Liver transplant recipients Documented or suspected HCC by imaging or liver biopsy Evidence of a medical condition associated with chronic liver disease other than HCV (such as but not limited to: hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures) History of chronic hepatitis B virus (HBV) as documented by HBV serologies (eg. HBsAg-seropositive). Patients with resolved HBV infection may participate (eg. HBsAb-seropositive) 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 enrollment

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: Arm 1 - BMS-791325 plus peg-interferon alfa-2a and ribavirin<br> | Drug: BMS-791325<br>* Tablets, Oral, 75 mg, twice daily, 4-48 weeks depending on response<br>Drug: Peg-interferon alfa-2a<br>* Syringe, Subcutaneous Injection, 180 µg, once weekly, 4-48 weeks depending on response<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 4-48 weeks depending on response<br>* Other names: Copegus;|
| Experimental: Arm 2 - BMS-791325 plus peg-interferon alfa-2a and ribavirin<br> | Drug: BMS-791325<br>* Tablets, Oral, 150 mg, twice daily, 4-48 weeks depending on response<br>Drug: Peg-interferon alfa-2a<br>* Syringe, Subcutaneous Injection, 180 µg, once weekly, 4-48 weeks depending on response<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 4-48 weeks depending on response<br>* Other names: Copegus;|
| Placebo Comparator: Arm 3 - Placebo plus peg-interferon alfa-2a and ribavirin<br> | Drug: Placebo<br>* Tablets, Oral, 0 mg, twice daily, 4-48 weeks depending on response<br>Drug: Peg-interferon alfa-2a<br>* Syringe, Subcutaneous Injection, 180 µg, once weekly, 4-48 weeks depending on response<br>* Other names: Pegasys;Drug: Ribavirin<br>* Tablets, Oral, 1000 or 1200 mg based on weight, twice daily, 4-48 weeks depending on response<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) |  | Formal analysis at week 4 (and upon occurrence) | 
| Safety, as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Formal analysis at week 12 (and upon occurrence) | 
| Safety, as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Formal analysis at week 24 post treatment (and upon occurrence) | 
| Safety, as measured by the frequency of serious adverse events (SAEs) and discontinuations due to adverse events (AEs) |  | Formal analysis at week 48 post treatment (and upon occurrence) | 
| Antiviral activity, as determined by the proportion subjects with eRVR |  | Week 4 | 
| Antiviral activity, as determined by the proportion subjects with eRVR |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with rapid virologic response (RVR), defined as undetectable HCV RNA |  | Week 4 | 
| Proportion of subjects with complete early virologic response (cEVR), defined as undetectable HCV RNA |  | Week 12 | 
| Proportions of subjects with a 12-week SVR (SVR12) and 24-week SVR (SVR24), defined as undetectable HCV RNA at off treatment follow-up |  | Week 12 | 
| Proportions of subjects with a 12-week SVR (SVR12) and 24-week SVR (SVR24), defined as undetectable HCV RNA at off treatment follow-up |  | Week 24 | 
| Resistant HCV variants associated with virologic failure |  | End of treatment (Week 48) or upon early discontinuation |