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

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;