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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
Box Hill Hospital
Box Hill, Victoria, Australia
Monash Medical Centre
Clayton, Victoria, Australia
St Vincent's Hospital
Fitzroy, Victoria, Australia
Western Hospital
Footscray, Victoria, Australia
Early viral kinetics
Determined by plasma HCV RNA quantification at frequent time points - baseline, day 1, 2, 3, 4 and 5
Time frame: Day 5
Rates of virological response
Percentage of patients with undetectable plasma HCV RNA) at different time-points
Time frame: Day 3, 5, week 2, week 4, week 12 and end of treatment (week 24 or week 48)
Number of patients eligible for Response Guided Therapy
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 therapy
Time frame: Week 4 and week 20
Rates of virological breakthrough
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.
Time frame: Week 4, week 20, week 24, week 48, week 60
Rates of SVR12 and relapse
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 treatment
Time frame: Week 48 and Week 60
Rates of anaemia on treatment
Time frame: Day 0, 1, 2, 3, 4, 5, then monthly up to week 48 of treatment
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