Safety and Efficacy of the Therapeutic Vaccine GI-5005 Combined With Pegylated Interferon Plus Ribavirin Standard of Care Therapy Versus Standard of Care Alone in Patients With Genotype 1 Chronic Hepatitis C Infection

A Phase 2 Randomized, Open Label, Multi-center, Therapeutic Trial of the Efficacy, Immunogenicity, and Safety of GI-5005; an Inactivated Recombinant Saccharomyces Cerevisiae Expressing a Hepatitis C Virus NS3-Core Fusion Protein, Combined With Pegylated Interferon Plus Ribavirin Standard of Care Therapy Versus Standard of Care Alone, and GI-5005 Salvage of Standard of Care Failures, in Patients With Genotype 1 Chronic Hepatitis C Infection

The GI-5005 therapeutic vaccine in combination with standard of care or standard of care alone will be injected under the skin of HCV subjects. Patients will be monitored for safety, immune responses and any therapeutic benefits related to the injections including EVR, ETR, and SVR.

Inclusion Criteria:

• Chronic hepatitis C infection with genotype 1 based on serum positivity for HCV RNA or a positive test for serum anti-HCV antibody for at least 6 months;
• One of the following response criteria based on response to prior combination therapy with pegylated or non-pegylated interferon plus ribavirin:

Non-Responders

• Poor responders - a subset of non-responders who achieved > 1 log10 but < 2 log10 reduction in HCV RNA after a minimum of 12 weeks of prior interferon based therapy.
• Partial responders - a subset of non-responders who achieve at least a 2 log10 reduction in HCV RNA by 12 weeks, but do not achieve an end of treatment response (ETR defined as HCV RNA negativity by PCR assay at the end of a minimum of 6 months of therapy).

Naive

• Patients who are treatment naïve and have refused IFN therapy for reasons other than contraindication.
• Signed, written, informed consent from the patient or legal representative before any study-specific procedures are performed;
• Liver biopsy within 3 years of the screening visit, documenting extent of liver disease consistent with chronic hepatitis C with evidence of inflammation and/or fibrosis. Liver biopsy within 1 year for subjects consenting to paired biopsy testing. Eight unstained liver biopsy slides are required for the baseline sample and post-treatment sample for use in central blinded evaluation for paired biopsy testing;
• Age ≥ 18 years;
• Negative scratch test (immediate hypersensitivity, IgE mediated) to S. cerevisiae.

Exclusion Criteria:

• History of decompensated liver disease, including but not restricted to, portal hypertension as manifested by a known history of gastroesophageal varices, variceal bleeding, ascites or encephalopathy, histopathologic or clinical evidence of cirrhosis, hepatocellular carcinoma, or renal impairment consistent with hepatorenal syndrome;
• History of significant non-HCV chronic liver disease, i.e. alcoholic hepatitis, autoimmune hepatitis;
• Null response to prior IFN plus ribavirin therapy, defined as patients that have received at least 12 weeks of interferon-based treatment with < 1 log10 reduction in viral load;
• Subjects treated with more than 1 complete hepatitis C regimen (subjects with a history of 1 complete prior regimen and a second incomplete prior regimen may be eligible upon discussion with and approval of the medical monitor);
• Subjects that required a dose reduction of >25% of the planned exposure of IFN or >50% of their planned ribavirin exposure during their previous interferon/ribavirin treatment;
• Subjects that required growth factors during their previous interferon/ribavirin treatment;
• Subjects that received small molecule inhibitor therapy combined with an interferon based regimen. (subjects that received small molecule inhibitor monotherapy can be included);
• Treatment for HCV infection within 28 days before screening;
• Chronic hepatitis B infection or positive hepatitis B surface antigen (HBsAg) at screening;
• Body weight >275 pounds;
• Known history of HIV infection or positive HIV antibody test at screening;
• History of Crohn's disease or ulcerative colitis;
• Concurrent therapy with herbal supplements taken specifically for the treatment of HCV (i.e. milk thistle). Wash-out of HCV related herbals for 28 days prior to Day 1. Consult sponsor before excluding potential subjects;
• Alcohol and/or IV drug abuse within the past year;