Combination Therapy for Chronic Hepatitis C Infection

• INCLUSION CRITERIA:
• Eighteen years of age or older at screening.
• Female study participants with childbearing potential (as defined below) and all males must be willing to practice either:
• Abstinence from sexual intercourse or
• One or more forms of effective barrier contraception throughout dosing and for 30 days following the last dose. This cannot include hormonal contraception for female subjects.

Effective forms of barrier contraception include:

• a male condom with spermicide
• use by female sexual partner of a female condom with spermicide

Non-childbearing potential (i.e., physiologically incapable of becoming pregnant) includes any female who:

• Has had a hysterectomy or
• Has had a bilateral oophorectomy (ovariectomy) or
• Is post-menopausal (a demonstration of a total cessation of menses for greater than or equal to1 year)
• Has had a bilateral tubal ligation or fallopian tube inserts
• Chronic HCV GT-1 or GT-4 infection as documented by greater than or equal to 1 measurement of serum HCV RNA greater than or equal to 2,000 international units per milliliter during screening and at least one of the following:
• A positive anti-HCV antibody, HCV RNA, or HCV genotype test result greater than or equal to 12 months prior to the baseline (day 0) visit together with current positive HCV RNA and anti-HCV antibody test results or
• Positive HCV RNA test and anti-HCV antibody test results together with a liver biopsy consistent with chronic HCV infection or a liver biopsy performed before enrollment with evidence of chronic hepatitis C infection disease, such as the presence of fibrosis.
• Group A may include up to 20% of subjects with compensated cirrhosis.

Group B and C may only include subjects with absence of cirrhosis.

Group D, D-ReTx & E may include subjects with compensated cirrhosis.

Group F may only include patients with advanced liver disease (historic Metavir or HAI Stage 3 or 4 or ISHAK Stage 4, 5 or 6 or cirrhosis as defined below)

Group G and H may only include those with absence of cirrhosis and HAI Stage 0-2 or FibroTest as below.

Cirrhosis is defined as any one of the following:

• Any biopsy showing cirrhosis.
• A FibroTest(r) score of greater than or equal to 0.75 AND an AST: platelet ratio (APRI) of > 2 performed within 12 months of screening.

Liver imaging within 6 months of Day 0 to exclude hepatocellular carcinoma (HCC) is required in patients with cirrhosis.

Absence of cirrhosis is defined as one of the following:

• A liver biopsy performed within 36 calendar months of screening showing absence of cirrhosis.
• A FibroTest(r) score of moderate non-alcoholic steatohepatitis and toxin exposures).
• Use of herbal/natural remedies for potential benefit to the liver within 21 Days of Day 0.
• History of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease.
• Screening or baseline ECG with clinically significant ECG findings, or a personal/first degree relative history of Torsade de pointes.
• Abnormal hematological and biochemical parameters at screening, including:
• Neutrophil count less than 750 cells per cubic millimeter.
• Hemoglobin level < 9 g/dL. If Hgb < 11g/dL in women and < 12 g/dL in men other causes of anemia should be excluded as medically indicated.
• Platelet count less than or equal to 50,000 cells per cubic millimeter.
• Estimated glomerular filtration rate less than 50 milliliter/min/1.73m(2).
• ALT or AST level greater than or equal to 10 times upper limit of normal (ULN).
• Serum lipase level greater than or equal to 1.5 times upper limit of normal (ULN)at screening or during the screening period in a patient with symptoms consistent with pancreatitis.
• Total bilirubin level greater than or equal to 2.0 times upper limit of normal (ULN), except in subjects with Gilbert s syndrome.
• Albumin level less than or equal to 3.0 grams per deciliter in patients without cirrhosis, albumin less than or equal