Study of SCY-635, Pegasys and Copegus in Hepatitis C
Condition: Hepatitis C Infection
MeSH terms: Infections; Hepatitis A; Hepatitis C; Hepatitis
Intervention: Placebo; SCY-635; Pegasys; Copegus
Intervention description: Oral tablets given bid for 28 days; SCY-635 tablets, 300 mg bid for 28 days; 180 ug prefilled syringe given once per week for up to 48 weeks; tablets given bid for up to 48 weeks
Intervention MeSH terms: Peginterferon alfa-2a
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hepatitis C; SCY-635; Ribavirin; Interferon

Summary:

      This study will examine the effectiveness of 28 days of triple combination therapy including
      SCY-635 with peginterferon alfa 2a and ribavirin in reducing serum HCV RNA levels. An
      additional 20 weeks of treatment with the currently approved standard of care will be offered
      to all participants. The Week 24 visit will be the last on-study visit. After the Week 24
      visit, all subjects with undetectable HCV RNA will be given the option to continue treatment
      with standard of care for an additional 24 weeks (out to Week 48) under the care of their
      Principal Investigator.
    

Eligibility criteria:

        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