Antifibrotic Activity Of GI262570 In Chronic Hepatitis C Subjects

Inclusion criteria

• A subject will be eligible for inclusion in this study only if all of the following criteria apply:
• Age between 40 and 70 years, inclusive.
• Documented positive serology for HCV antibody by a second generation or higher assay.
• Serum HCV RNA positive and HCV viral Genotype 1 at pre-screening visit.
• Ishak fibrosis score of 2, 3 or 4.
• Failure to achieve sustained virologic response (SVR) with previous interferon (standard or pegylated) and ribavirin treatment administered at a minimum dose of 3mU three times weekly or equivalent, for at least 12 weeks. Reasons for failure may include failure to respond to treatment or intolerability to optimal treatment. Prior treatment with interferon/ribavirin must have been discontinued at least 11 months prior to the biopsy date.
• Male or female; a female is eligible to enter and participate in this study if she is of:
• non-childbearing potential (i.e., physiologically incapable of becoming pregnant, including any female who is post-menopausal); or,
• child-bearing potential, has a negative serum pregnancy test at screen, and agrees to one of the following:
• Complete abstinence from intercourse from 2 weeks prior to administration of the study drug, throughout the study, and for a time interval after completion or premature discontinuation from the study to account for elimination of the investigational drug, (a minimum of 5 half-lives or longer if the pharmacodynamic profile of the investigational drug warrants a longer time period); or,
• Female sterilization; or,
• Has a male partner who is sterilized; or,
• Implants of levonorgestrel; or,
• Injectable progestogen; or,
• Oral contraceptive (combined or progestogen only) , must be stable for 3 months prior to study entry; or,
• Any intrauterine device (IUD) with published data showing that the lowest expected failure rate is less than 1% per year (not all IUDs meet this criterion); or,
• Any other methods with published data showing that the lowest expected failure rate for that method is less than 1% per year; or,
• Barrier method only if used in combination with any of the above acceptable methods.
• Availability and willingness of subject to provide written informed consent.

Exclusion criteria

A subject will not be eligible for inclusion in this study if any of the following criteria apply:

• History of ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis or other signs of hepatic decompensation.
• Current or historical evidence suggestive of ischemic heart disease or other cardiovascular disease that in the investigator's opinion may adversely impact the safety of the subject during the conduct of the study. Evidence suggestive of cardiovascular disease may come from a number of sources, including clinical history, physical exam, electrocardiogram, laboratory testing, and radiographic procedures.
• New York Heart Association (NYHA) Functional Class 1, 2, 3, or 4 cardiac status
• Co-infection with HBV or HIV.
• Liver histology consistent with any other co-existing cause of chronic liver disease.
• Documented evidence of a hepatic mass lesion suspicious for hepatocellular carcinoma.
• Alpha-fetoprotein > 200ng/mL at pre-screening.
• Inadequate hematologic function defined by any of the following:

Hemoglobin ( 1.5mg/dL (≥130mmol/L)) Calculated creatinine clearance as calculated by Cockcroft and Gault ( 1.2 x ULN.

• Prothrombin time > 15 seconds or International normalized ratio (INR) > 1.3.
• Organ, stem cell, or bone marrow transplant.
• Serious concurrent medical illness that in the investigator's opinion might interfere with therapy. This includes significant systemic illnesses (other than liver disease) such as chronic pancreatitis.
• Active systemic autoimmune disorder.
• A pre-existing condition interfering with normal gastrointestinal anatomy or motility, and/or renal function that could interfere with the absorption, metabolism, and/or excretion of the s