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

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

An Open-Label, 3-Panel, Dose-Escalation Study to Assess the Safety and Tolerability, Pharmacokinetics, and Viral Kinetics of Two Doses of LocteronTM (Poly ActiveTM - Interferon Alpha 2b) Given Every 2 Weeks for 4-12 Weeks in Comparison With PEG-Intron Given Weekly for 4-12 Weeks in Patients With Chronic Hepatitis C

The purposes of the PLUS study were to confirm the safety and tolerability of two doses of LocteronTM (320 ug and 640 ug) dosed over four weeks in patients who had failed prior anti-HCV therapies (Panels A and B), and then to continue to study the safety, tolerability, and preliminary efficacy of the same two doses of LocteronTM (320 ug and 640 ug) in treatment-naïve genotype 1 HCV patients when Locteron dosed over 12 weeks (Panel C). All subjects were also to receive oral daily weight-based ribavirin.

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.

Antimetabolites, Virus Diseases, Anti-Infective Agents, RNA Virus Infections, Digestive System Diseases, Flaviviridae Infections, Antineoplastic Agents, Therapeutic Uses, Antiviral Agents, Molecular Mechanisms of Action, Pharmacologic Actions

Bi-weekly subcutaneous doses of Locteron (controlled-release interferon alpha 2b) with oral ribavirin.

Bi-weekly subcutaneous doses of Locteron (controlled-release interferon alpha 2b) with oral ribavirin.

Weekly subcutaneous injections of 1.5 ug/kg PegIntron (12 kDalton pegylated interferon alpha 2b) with oral ribavirin.

To assess in subjects with chronic hepatitis C the safety and tolerability of Locteron in comparison with PEG-Intron.

To assess in subjects with chronic hepatitis C receiving a weight-based oral daily dose of ribavirin: • The PK profile of Locteron (IFNa2b) • The preliminary efficacy of Locteron assessed by serial quantitation of HCV RNA levels

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

Lawitz E, Younossi ZM, Shiffman M, Gordon S, Ghalib R, Long W, Muir A, McHutchison J. Randomized trial comparing systemic and local reactions to controlled-release interferon alpha2b and pegylated-interferon alpha2b in hepatitis C subjects who failed prior treatment. J Hepatology 50:S231 (abstract 628), 2009. (Presented to the 44th Annual Meeting Of The European Association for the Study of the Liver, April 22-26, 2009.)