A Pilot Study of Boceprevir for the Treatment of Genotype 6 HCV
A Pilot Study of Boceprevir for the Treatment of Genotype 6 HCV
The purpose of this study is to evaluate the antiviral efficacy of Boceprevir-based therapy
 for the treatment of genotype 6 chronic hepatitis C infection.

 Boceprevir has recently been approved for the treatment of genotype 1 chronic hepatitis C
 infection. Recent in vitro studies suggest similar efficacy against genotype 6 chronic
 hepatitis C infection.

 The investigators therefore hypothesise that:

 i) Boceprevir is a potent inhibitor of genotype 6 hepatitis C replication in vivo.

 ii) Boceprevir in combination with pegylated interferon-alpha and ribavirin for 24 weeks will
 cure a high proportion of patients chronically infected with genotype 6 chronic hepatitis C
 infection.
Genotype 6 HCV (HCV-6) is common in parts of South-East Asia, in particular Vietnam. There is
 a small but growing population of immigrant patients with chronic HCV-6 in Australia. The
 current standard-of-care treatment (SOC) for chronic HCV-6 infection is peg-interferon-α
 (PEG-IFN) and ribavirin (RBV) therapy for 48 weeks. The available data evaluating treatment
 outcome suggests that SVR rates are intermediate between those of HCV-1 and HCV-2/3. There is
 a medical need for novel therapies that might increase SVR rates and/or allow shortened
 treatment duration.

 Boceprevir is a novel HCV NS3 protease inhibitor, and boceprevir-based triple therapy has
 recently been approved for the treatment of HCV-1. Boceprevir also appears to have some
 antiviral effect against HCV-2 and HCV-3 in vivo. Boceprevir has not been used to treat
 patients with chronic HCV-6 infection. Recent in vitro data have demonstrated that boceprevir
 has an antiviral effect against HCV-6.

 The investigators are therefore undertaking an investigator-initiated proof-of-concept pilot
 study of boceprevir-based therapy for the treatment of patients chronically infected with
 HCV-6.

 The study population will consist of a representative group of 30 adult patients who are
 chronically infected with genotype 6 HCV. All patients will be of Asian background, will be
 non-cirrhotic, and will carry a "good response" IL28B genotype (C/C for rs12979860). The
 patients will be recruited from the outpatient clinics of 4 Hepatology units in Melbourne,
 Australia, represented by the principal and associate investigators.
Inclusion Criteria:

 -  Male or female, at least 18 years of age

 -  Asian background

 -  HCV treatment-naïve.

 -  Chronic HCV infection is defined as one of the following:

 -  Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before Screening, and
 positive for HCV RNA and anti-HCVAb at the time of Screening; or

 -  Positive for anti-HCV Ab and HCV RNA at the time of Screening with a liver biopsy
 consistent with chronic HCV infection (or a liver biopsy performed prior to enrollment
 with evidence of chronic hepatitis C disease).

 -  Screening laboratory result indicating HCV genotype 6-infection (HCV-6).

 -  Plasma HCV RNA level > 10,000 IU/mL at Screening.

 -  IL28B C/C genotype (rs12979860)

 -  Per local standard practice, documented results of one of the following:

 -  A liver biopsy within 24 months prior to or during screening demonstrating the absence
 of cirrhosis, e.g., a METAVIR Score of 3 or less, Ishak score of 4 or less; or

 -  A screening FibroTest score of ≤ 0.72 and Aspartate Aminotransferase to Platelet Ratio
 Index (APRI) ≤ 2; or

 -  A screening FibroScan result of < 9.6 kPa.

 -  Subjects with a non-qualifying Fibrotest/APRI or Fibroscan result may only be enrolled
 if they have a qualifying liver biopsy preformed within 24 months prior to or during
 screening.

 -  Candidate for PEG/RBV therapy

 -  Body mass index (BMI) between 18 and 36 kg/m2

 -  Agree to use two highly effective methods of avoiding contraception for the duration
 of the study and for 7 months after the last dose study medication. Females of
 childbearing potential must have negative pregnancy test at Screening and Baseline

 -  Provide written informed consent to participate in the study.

 -  Subjects must have the following laboratory parameters at Screening:

 -  ALT ≤ 10 × the upper limit of normal (ULN)

 -  AST ≤ 10 × ULN

 -  Hemoglobin ≥ 12 g/dL

 -  White blood cell count ≥ 2,500 cells/μL

 -  Absolute neutrophil count (ANC) ≥ 1,500 cells/mm3

 -  Platelets ≥ 90,000/mm3

 -  Prothrombin time ≤ 1.5 × ULN

 -  Albumin > 3 g/dL

 -  Direct (conjugated) bilirubin < ULN

 -  Thyroid stimulating hormone (TSH) ≤ ULN

 -  Creatinine clearance (CLcr) ≥ 50 mL/min, as calculated by the Cockcroft-Gault equation

 Exclusion Criteria:

 -  Non-genotype 6 HCV infection, or evidence of mixed genotype HCV infection

 -  IL28B C/T or T/T polymorphism (rs12979860)

 -  Any current or past clinical evidence of cirrhosis such as ascites or esophageal
 varices, or prior biopsy showing cirrhosis, e.g., a Metavir Score of >3 or Ishak score
 of > 4.

 -  Exceed defined thresholds for key laboratory parameters at Screening.

 -  Females who are pregnant or plan to become pregnant, or breastfeeding, or males whose
 partners are pregnant or planning to become pregnant within 7 months (or per local RBV
 label) after their last dose of study drug.

 -  Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human
 immunodeficiency virus antibody (HIV Ab).

 -  Diagnosis of autoimmune disease, decompensated liver, disease, poorly controlled
 diabetes mellitus, significant psychiatric illness, severe chronic obstructive
 pulmonary disease (COPD), hepatocellular carcinoma or other malignancy (with exception
 of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed

 -  Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin),
 or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance
 treatment for at least 6 months prior to Screening may be included into the study.

 -  Use of prohibited concomitant medications two weeks prior to baseline through the end
 of treatment, as defined by the product label.