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.
Name: Victrelis® (boceprevir) 800mg by mouth, TID (200 mg tablets)
Name: Peg-Intron® (peginterferon-α-2b), 1.5ug/kg sc injection
Name: Rebetol® (ribavirin), 1000/1200mg by mouth daily
Description: Determined by plasma HCV RNA quantification at frequent time points - baseline, day 1, 2, 3, 4 and 5Measure: Early viral kinetics Time: Day 5
Description: Percentage of patients with undetectable plasma HCV RNA) at different time-pointsMeasure: Rates of virological response Time: Day 3, 5, week 2, week 4, week 12 and end of treatment (week 24 or week 48)
Description: Patients in Arm A and B randomised to received boceprevir-based triple therapy who achieve an undetectable HCV PCR at week 4 and week 20 are eligible for 24 weeks of therapy, vs. 48 weeks of therapyMeasure: Number of patients eligible for Response Guided Therapy Time: Week 4 and week 20
Description: Defined by an increase in HCV RNA > 1 log10 IU/mL from nadir, or HCV RNA increase to > 100 IU/mL in patients who had previously reached an undetectable HCV RNA, and confirmed by 2 consecutive samples < 4 weeks apart.Measure: Rates of virological breakthrough Time: Week 4, week 20, week 24, week 48, week 60
Description: SVR 12 - Number of patients who achieve an undetectable HCV PCR 12-weeks post treatment Relapse - Number of patients who have an undetectable HCV PCR at the end of treatment but detectable HCV PCR 12-weeks post treatmentMeasure: Rates of SVR12 and relapse Time: Week 48 and Week 60
There is one SNP
- 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 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.
All patients will be of Asian background, will be non-cirrhotic, and will carry a "good response" IL28B genotype (C/C for rs12979860).