Safety, Tolerability, and Antiviral Activity of ANA598 Administered in Combination With Pegylated Interferon and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability and effectiveness of ANA598 when administered with pegylated interferon and ribavirin (Standard of Care [SOC]) compared to placebo + SOC.

Detailed Description
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The safety, tolerability and antiviral activity of ANA598, administered orally at 200 mg BID or 400 mg BID for 12 weeks in combination with pegylated interferon and ribavirin (SOC) will be compared to placebo + SOC. Treatment-naïve patients with genotype 1 infection will be eligible for enrollment. Patients randomized to ANA598 will receive a loading dose of 800 mg q 12 hours administered on the first day of dosing. Patients with undetectable HCV RNA at week 4 and week 12 will be randomized to receive either an additional 12 or 36 weeks of SOC alone. Ninety patients will be randomized into 2 cohorts. The forty-five patients in each cohort will be randomized as 30 active: 15 placebo.

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

Conditions
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HCV Infection

Intervention / Treatment
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* Drug: placebo
* Drug: ANA598
* Drug: ANA598
* Drug: Peginterferon
* Drug: Ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, ages 18 to 65 years Documented chronic HCV infection, genotype 1a or 1b Treatment-naïve Exclusion Criteria: Female patients who are pregnant or breast-feeding Infection with non-genotype 1 HCV Previous treatment for HCV infection HIV or HBV positive Any medical contraindication to Peg-IFN or RBV therapy History of any other known cause of liver disease

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1<br>Peginterferon and ribavirin + placebo BID for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks | Drug: placebo<br>* oral BID<br>Drug: Peginterferon<br>* 180 μg dose via subcutaneous injection weekly<br>Drug: Ribavirin<br>* oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg<br>|
| Experimental: 2<br>ANA598 200 mg BID + Peginterferon and ribavirin for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks | Drug: ANA598<br>* oral 200mg BID<br>Drug: Peginterferon<br>* 180 μg dose via subcutaneous injection weekly<br>Drug: Ribavirin<br>* oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg<br>|
| Experimental: 3<br>ANA598 400mg BID + Peginterferon and ribavirin for 12 weeks, followed by Peg-IFN and RBV for an additional 12 or 36 weeks | Drug: ANA598<br>* oral 400mg BID<br>Drug: Peginterferon<br>* 180 μg dose via subcutaneous injection weekly<br>Drug: Ribavirin<br>* oral 1000 mg/day for patients who weighed < 75 kg and 1200 mg/day for patients who weighed ≥ 75 kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Undetectable HCV RNA |  | 12 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability |  | Throughout study | 
| Undetectable HCV RNA |  | Week 4, Week 24, and Week 48 | 
| ANA598, Peg-IFN-a-2-a, ribavirin concentrations |  | Various time points through Week 12 | 
| Undetectable HCV RNA |  | 24 weeks after completion of therapy for sustained virologic response [SVR] |