A Study of Setrobuvir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients With Genotype 1 Chronic Hepatitis C

Study Overview
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Brief Summary
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This randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of setrobuvir in patients with genotype 1 chronic hepatitis C. Treatment-naïve patients will be randomized to receive either setrobuvir (800 mg orally b.i.d loading dose followed by 200 mg orally .b.i.d.) or placebo in combination with standard of care Pegasys (peginterferon alfa-2a) and Copegus (ribavirin). Treatment duration will be 28 weeks or 48 weeks depending on response. Treatment-experienced patients categorized as relapsers, partial responders and viral breakthrough patients to previous pegylated interferon and ribavirin therapy will be randomized to receive either setrobuvir or placebo in combination with Pegasys and Copegus for 48 weeks. Treatment-experienced patients categorized as null-responders to previous pegylated interferon and ribavirin therapy will be assigned to treatment with setrobuvir plus Pegasys and Copegus for 48 weeks.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled Trial of the Safety and Efficacy of ANA598 Administered With Pegylated Interferon and Ribavirin in Genotype 1 Patients With Chronic Hepatitis C Infection

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: peginterferon alfa-2a [Pegasys]
* Drug: placebo
* Drug: ribavirin [Copegus]
* Drug: setrobuvir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients, 18 to 65 years of age inclusive Documented chronic hepatitis C Treatment-naïve (no prior exposure to Pegasys, Copegus, or experimental HCV therapy) or treatment-experienced with current standard of care (Pegasys and Copegus) but categorized as null-responder or patients with partial response, relapse or viral breakthrough during or following prior treatment Serum HCV RNA >/= 50,000 IU/mL at screening HCV antibody positive at screening HCV genotype 1 Body mass index (BMI) 18-38 kg/m2 In good health other than chronic HCV infection in the judgment of the principal investigators Negative for hepatitis B and HIV infection Exclusion Criteria: Pregnant or breastfeeding women For treatment-naïve patients: any previous treatment for HCV infection For treatment-experienced patients: previous treatment with an experimental therapy for HCV infection Co-infection with HIV or hepatitis C virus (HBV) History or evidence of decompensated liver disease History or evidence of hepatocellular carcinoma History of alcohol abuse and/or other drug addiction </= 1 year prior to enrollment in the study Poorly controlled diabetes mellitus One or more additional known primary causes of liver disease other than hepatitis C History of acute or chronic pancreatitis Participation in an other clinical study of a new chemical entity within 30 days prior to study randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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 |
| --- | --- |
| Active Comparator: Active Comparator<br>Pplacebo in combination with standard of care Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly<br>Drug: placebo<br>* Orally b.i.d.<br>Drug: ribavirin [Copegus]<br>* 1000 mg or 1200 mg orally daily<br>|
| Experimental: Setrobuvir<br>Setrobuvir (800 mg orally b.i.d loading dose followed by 200 mg orally .b.i.d.) in combination with standard of care Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) | Drug: peginterferon alfa-2a [Pegasys]<br>* 180 mcg sc weekly<br>Drug: ribavirin [Copegus]<br>* 1000 mg or 1200 mg orally daily<br>Drug: setrobuvir<br>* Loading dose of 800 mg orally b.i.d on Day 1, followed by 200 mg orally b.i.d., 28 or 48 weeks<br>* Other names: ANA598;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving sustained virologic response (SVR24), defined as undetectable hepatitis C virus (HCV) RNA at 24 weeks after discontinuation of all study drugs |  | 24 weeks after discontinuation of all study drugs (treatment duration 28 or 48 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving undetectable HCV RNA (defined as HCV RNA < 15 IU/mL) at each visit through Week 24 |  | 24 weeks | 
| Proportion of treatment-naïve patients eligible to stop all treatment at Week 28 |  | 28 weeks | 
| Safety: Incidence of adverse events |  | up to approximately 72 weeks |