Study of SCY-635, Pegasys and Copegus in Hepatitis C

Inclusion Criteria:

• Quantifiable serum levels of HCV-specific RNA in excess of 100,000 IU/mL
• Chronic HCV status
• HCV genotype 1 infection and IL28B genotype of C/T or T/T

• Liver biopsy results within 3 years prior to screening indicating the absence of cirrhosis

  *If no previous biopsy is available, a biopsy must be performed during the screening period to qualify for randomization

• Body mass index (BMI) between 18 and 38 kg/m2

• Laboratory variables within acceptable ranges:

  • ALT/AST < 3 × ULN;
  • HgB > 12g/dL for females, > 13 g/dL for males;
  • total WBC count > 3000/mm3 and ANC > 1500/mm3;
  • platelets > 100,000/mm3;
  • prothrombin time (or INR) ≤ 1.2 × ULN;
  • serum albumin ≥ 3.4 g/dL;
  • total bilirubin WNL;
  • serum creatinine WNL; if serum creatinine is > ULN, then calculated creatinine clearance must be > 100 mL/min (by Cockcroft-Gault formula) for subject to be eligible
• Subjects of childbearing potential (i.e., not surgically sterile or postmenopausal) must agree to use 2 forms of contraception from Screening until 24 weeks after completion of treatment with RBV
• Negative urine testing for amphetamines and cocaine at Screening.
• If female, the subject has a negative pregnancy test at Screening and on study Day 1

Exclusion Criteria:

• History of clinically significant gastrointestinal, renal, hepatic, neurologic, hematologic, endocrine, oncologic, pulmonary, immunologic, psychiatric, or cardiovascular disease
• Females who are pregnant or breastfeeding
• Males with partners who are pregnant or are planning to become pregnant
• HCV genotype other than genotype 1 and an IL28B genotype of C/C
• Seropositive for HIV-1 or HIV-2 or hepatitis B virus (HBV) surface antigen (HBsAg)
• Use of any investigational agent within 3 months prior to dosing
• Received any prior FDA-approved or investigational drug or drug regimen for the treatment of hepatitis C
• Evidence of cirrhosis on a previous liver biopsy
• Evidence of decompensated liver disease
• Recipient of an organ transplant
• Evidence of hepatocellular carcinoma
• Evidence of ongoing alcohol or substance abuse
• Poorly-controlled diabetes mellitus
• Congestive heart failure or unstable cardiopulmonary condition, renal disease, or hemoglobinopathy (sickle cell anemia or thalassemia
• History of seizure disorder
• History of severe psychiatric illness, including severe depression, history of suicidal ideation, suicidal attempts, related hospitalizations, bipolar disorder, or psychosis requiring medication
• Concurrent medical condition or laboratory abnormality that would constitute a contra-indication for interferon use
• History of unstable thyroid disease that would preclude administration of interferon-based therapy
• Medical condition that requires use of systemic corticosteroids
• Received warfarin or other anticoagulants during the 21 days immediately prior to Screening, or is expected to require warfarin or other anticoagulants during the study.
• One or more additional known primary or secondary causes of liver disease, other than hepatitis C
• Any other concurrent medical condition likely to preclude compliance with the schedule of evaluations, or likely to confound the efficacy or safety observations

• 12-lead ECG showing the following:

  • Corrected QTc interval ≥ 450 msec (Bazett's correction);
  • QRS > 120 msec;
  • Clinically significant abnormalities;
• Severe retinopathy or other significant ophthalmological disorder
• Use of any herbal supplements within 28 days prior to dosing.
• The use of CYP3A inducers or inhibitors for at least 2 weeks prior to initiation of treatment through Week 6