Safety and Efficacy of ANA598 Administered With Pegylated Interferon and Ribavirin in Genotype-1 Patients With Chronic HCV Infection

• Undetectable HCV RNA [ Time Frame: 24 Weeks ] [ Designated as safety issue: No ]
  Assess the comparative proportion of patients achieving undetectable HCV RNA (defined as HCV RNA <15 IU/mL) at each visit through Week 24
• SVR 12 [ Time Frame: 12 weeks after completing therapy ] [ Designated as safety issue: No ]
  Defined as undetectable HCV RNA 12 wks after completing treatment
• Proportion of treatment-naive patients eligible to stop all treatment at Week 28 [ Time Frame: 28 Weeks ] [ Designated as safety issue: No ]
• Safety and tolerability of ANA598 [ Time Frame: 48 Weeks ] [ Designated as safety issue: Yes ]
  Assess the safety and tolerability of ANA598 co-administered with standard-of-care (SOC) during 28 or 48 weeks of treatment

Assess the safety and efficacy of ANA598 administered with Pegylated Interferon and Ribavirin in Genotype 1 Patients with Chronic Hepatitis C Infection.

Eligible patients with chronic hepatitis C infection (HCV genotype 1) will be randomized to treatment with 200 mg BID (total daily dose 400 mg) ANA598 or matching placebo, while receiving co-administered pegylated interferon and ribavirin (standard-of-care, SOC). All patients receiving ANA598 will receive a loading dose of 800 mg BID (total dose 1600 mg) on Day 1.

Treatment-Naïve Patients:

Enrollment will include approximately 133 treatment-naïve Genotype 1 patients with chronic HCV infection (100 randomized to receive ANA598 + SOC, and 33 randomized to receive matching placebo + SOC).

Treatment-naïve patients will be treated for either 28 weeks or 48 weeks, depending on response to treatment. Patients with undetectable HCV RNA at Week 8 and at subsequent visits will complete all treatment at Week 28.

Patients with Prior SOC Treatment (All will receive 48 Weeks of therapy):

Approximately 113 patients categorized as having prior relapse , prior partial response or prior viral breakthrough to previous treatment will be randomized to treatment with ANA598 200 mg BID + SOC or placebo + SOC (80 randomized to be treated with ANA598 + SOC, and 33 randomized to be treated with placebo + SOC).

Approximately 28 treatment-experienced patients categorized as null responders to previous treatment will be assigned treatment for 48 weeks with ANA598 200mg BID and co-administered pegylated interferon and ribavirin.

• Drug: Placebo
  Oral BID
• Drug: ANA598
  Oral 200mg BID
• Drug: Ribavirin
  Ribavirin
• Drug: Pegylated Interferon
  Pegylated Interferon

• Experimental: ANA598
  ANA598 200mg BID (28 or 48 Weeks) + co-administered pegylated interferon and ribavirin
  Interventions:

  • Drug: ANA598
  • Drug: Ribavirin
  • Drug: Pegylated Interferon
• Placebo Comparator: Placebo Comparator
  Matching ANA598 placebo (28 or 48 Weeks) + co-administered pegylated interferon and ribavirin
  Interventions:

  • Drug: Placebo
  • Drug: Ribavirin
  • Drug: Pegylated Interferon

Inclusion Criteria:

• Documented chronic hepatitis C infection, genotype 1 at screening
• Treatment-naïve; no prior exposure to pegylated interferon, ribavirin, or experimental HCV therapy
• Treatment-experienced patients including Partial responders, Prior relapse, Prior viral breakthrough, and Null responders; prior treatment with current standard of care (pegylated interferon alfa and ribavirin)

Exclusion Criteria:

• Female patients who are pregnant or breast feeding
• Infection with non-genotype 1 HCV
• For treatment-naïve patients: any previous treatment for HCV infection
• For treatment-experienced patients: previous treatment with any direct-acting antivirals for HCV infection
• Known HIV or HBV co-infection
• Any medical contraindications to Peg-INF or RBV therapy
• History of any other known cause of liver disease