HDV-Interferon in the Treatment of Chronic Hepatitis C Nonresponders and Naive Hepatitis C Patients

An Evaluation of Two Dose Routes of HDV-Interferon Administered With Ribavarin in the Treatment of Chronic Hepatitis C Nonresponders and Naive Hepatitis C Patients

A Phase II, Open Label, Multi-Center, Proof-Of-Concept Study determing whether treatment with HDV-Interferon (HDV-IFN), by oral or subcutaneous (injection) routes, and ribavirin results in similar efficacy [Rapid Virologic Response (RVR)] and safety as the reported efficacy and safety with pegylated alpha-interferon-2a and ribavirin (historical control) in patients with chronic hepatitis C (treatment naïve by oral route and non-responders by SC route respectively).

Part 1 ("initial part") - 4 weeks of treatment (28 days):

• All patients will complete an initial 4 weeks of treatment with HDV-Interferon (HDV-IFN) (treatment naïve by oral route and non-responders by SC route respectively) and ribavirin.
• The Part 1 of the study shall assess whether a 4-week treatment course with HDV-Interferon (HDV-IFN), orally or by subcutaneous injection, and ribavirin results similar efficacy [Rapid Virologic Response (RVR)] and safety as the reported efficacy and safety with pegylated alpha-interferon-2a and ribavirin (historical control) in patients with chronic hepatitis C (treatment naïve and non-responders).

Part 2 ("continuation part") - 44 or 20 weeks of treatment + 24 weeks (follow-up period):

• Patients with hepatitis C viral genotype 1, who achieve RVR, will be treated for another 44 weeks of therapy (to complete 48 weeks of active treatment) followed by 24 weeks of treatment-free follow-up period.
• Patients with hepatitis C viral genotype 3, who achieve RVR, will be treated for another 20 weeks of therapy (to complete 24 weeks of active treatment) followed by 24 weeks of treatment-free follow-up period.
• Follow-up period (24 weeks): Thus, in addition to treatment in Part 1 of study, each completed patient with viral genotype 1 will receive 44 weeks of therapy and 24 weeks of treatment-free follow-up; and viral genotype 3 patients will have 20 weeks of therapy & 24 weeks of treatment study drug free follow-up.
• Overall study duration (72 or 48 weeks): Patients with viral genotype 1 will have an overall study duration of 72 weeks (48 weeks of therapy plus 24 weeks follow-up) and patients with viral genotype 3 will have an overall study duration of 48 weeks (24 weeks of therapy plus 24 weeks follow-up).

Inclusion Criteria - Nonresponders:

• Patients >18 years with established chronic hepatitis C with viral genotype 1 or viral genotype 3 who have failed to respond to at least a 3-month course of a pegylated interferon alpha 2a + ribavirin and have a detectable HCV RNA and baseline liver biopsy available from within the prior 12 months.

Inclusion Criteria - Naive:

• Treatment naïve patients > 18 years, inclusive, are eligible for this study.
• Patients will be viral genotype 1 or viral genotype 3, have quantifiable HCV-RNA > 1000 IU/mL as demonstrated by PCR and an abnormal ALT (within 6 months of screening) and compensated liver disease with or without cirrhosis.

Exclusion Criteria - Nonresponders:

• Patients with decompensated cirrhosis or other forms of liver disease
• Hb < 10g/dL for males & Hb < 9 g/dl for females
• hepatocellular carcinoma
• active hepatitis B infection
• human immunodeficiency virus (HIV)
• pre-existing severe or uncontrolled depression or other psychiatric disease
• significant cardiac disease
• renal disease
• seizure disorders or retinopathy

Exclusion Criteria - Nonresponders:

• Patients with decompensated cirrhosis or other forms of liver disease
• Hb < 10g/dL for males & Hb < 9 g/dl for females
• hepatocellular carcinoma
• active hepatitis B infection
• HIV
• pre-existing severe or uncontrolled depression or other psychiatric disease - significant cardiac disease
• renal disease
• seizure disorders or retinopathy