Study of Safety, Tolerability, and Anti-Viral Effect of Locteron Compared to PEG-Intron in Patients With Chronic Hepatitis C

Panels A and B of the PLUS study were designed to assess the safety and tolerability, pharmacokinetics, and viral kinetics over four weeks of two doses of Locteron™ (230 ug and 640 ug) given every two weeks in comparison with PegIntron® given weekly in treatment-experienced subjects with chronic hepatitis C of any genotype who were co-administered weight-based oral ribavirin. The two cohorts of 16 subjects each in Panels A and B consisted of subjects who had failed prior interferon therapy. In Panel A, 8 subjects were randomized to and completed 4 weeks of treatment with 320 μg Locteron™ and 8 subjects were randomized to and completed 4 weeks of treatment with 1.5 ug/kg PegIntron®. In Panel B, 8 subjects were randomized to and completed 4 weeks of treatment with 640 μg Locteron™ and 8 subjects were randomized to and completed 4 weeks of treatment with 1.5 ug/kg PegIntron®. When the results of Panel A and Panel B were known, conduct of Panel C for 12 weeks in treatment-naive patients with chronic genotype-1 HCV was considered unnecessary and cancelled, and an entirely new study was begun instead.

Inclusion criteria

• Evidence of chronic hepatitis C
• Positive HCV RNA test with a level >= 1 x 104 IU/mL (by RT-PCR)

Exclusion criteria

• Decompensated Liver Disease
• Positive test for serum antibodies to the human immunodeficiency virus (HIV), hepatitis A (HAV-IgM), o hepatitis B (HBV- +Hepatitis B surface antigen)
• A history of severe psychiatric disease, including major depression
• A history of immunologically-mediated disease, COPD, severe asthma, severe cardiac disease, active cancer or cancer within last 5 years, seizures within the past 5 years or epilepsy, solid organ or bone marrow transplant, uncontrolled thyroid disease, or clinically significant retinopathy
• Pregnant or lactating females