Boceprevir-based Therapy to Rescue HCV Genotype 1/HBV Infected Patients Refractory to Combination Therapy
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of this study is to explore the efficacy and safety of boceprevir -based triple
      therapy to rescue HCV genotype 1 (HCV GT1)/HBV dually infected patients refractory to
      previous peginterferon (PEG-IFN) plus ribavirin (RBV) combination therapy.
    

Detailed description: 
      Liver disease, especially viral hepatitis, is an important public health issue, which
      frequent leads to liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related death.
      Around 340 to 400 million persons are infected with hepatitis B virus (HBV) and 130 to 210
      million persons are infected with hepatitis C virus (HCV) worldwide, In Taiwan, the
      prevalence of HBV infection is 15-20%, and the prevalence of HCV infection is 2-5% in general
      population. Moreover, there are some HCV-hyperendemic areas in southern Taiwan with anti-HCV
      prevalence rate of as high as 30-40%.

      HBV/HCV dual infections is not uncommon in HBV epidemic areas, such as Southeastern Asia,
      with a prevalence rate of 1.1% in southern Taiwan. Recent study showed that the risk of HCC
      incidence is even higher among HBV/HCV co-infected persons than those with HBV or HCV
      mono-infection, indicating the importance of disease control in this clinical setting.

      The PEG-IFN/RBV has been effective in the treatment of HCV-dominant, treatment-naïve patients
      with HCV/HBV dual infections. For treatment-naive HCV genotype 1 (HCV GT1)/HBV co-infected
      patients, 48 weeks of peginterferon (PEG-IFN) plus ribavirin (RBV) could achieve an HCV
      sustained virological response (SVR) rate of 72%, which was comparable to 77% for patients
      with HCV GT1 monoinfection. For treatment-naive HCV GT2 or GT3 /HBV co-infected patients, 24
      weeks of PEG-IFN plus RBV could achieve an HCV SVR rate of 83%, which was comparable to 84%
      for patients with HCV GT2/3 monoinfection . Furthermore, PEG-IFN plus RBV combination therapy
      could enhance seroclearance of hepatitis B surface antigen (HBsAg) with an HBsAg loss rate of
      upto 11%. Nevertheless, there is about 30% of HCV GT1/HBV and 20% of HCV GT2 or 3/HBV
      co-infected patients refractory to current PEG-IFN/RBV combination therapy, which remains at
      high risk of HCC and liver-related death.

      Boceprevir is an oral antiviral drug, which is NS3/4A protease inhibitor. Boceprevir has been
      approved for treating HCV GT1 infection by Food and Drug Administration (FDA) on 11 May 2011.
      For HCV GT1 mono-infected patients who refractory to previous PEG-IFN plus RBV combination
      therapy, becoprevir combined with PEG-IFN/RBV triple therapy can improve the treatment
      efficacy. The SVR rate of becoprevir-based triple therapy is about 3 times when compared to
      patients who received PEG-IFN with RBV dual therapy [14].The investigators , therefore,
      hypothesize that boceprevir plus PEG-IFN/RBV is effective in treating HCV GT1/HBV dually
      infected patients who are refractory to previous PEG-IFN/RBV combination therapy.
    

Intervention name(s): Stop trial intervention for boceprevir, PEG-IFN and RBV
Intervention type(s): Drug
Intervention description(s): Stop trial intervention for patients with 32 week therapy (arm A): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.
Stop trial intervention for patients with 48 weeks therapy (arm B): for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.
Stop trial intervention for for null responder or cirrhotic patients: (arm C) for all patients, if HCV RNA is more than 100 IU/ml at week 12 or HCV RNA is detectable at week 24, therapy will be stopped.
Other intervention name(s): Stop trial intervention for arm A; Stop trial intervention for arm B; Stop trial intervention for arm C
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hepatitis C virus; hepatitis B virus; boceprevir; null responder; partial responder; relapser