Safety, Tolerability, and Efficacy of Asunaprevir and Daclatasvir in Subjects Coinfected With HIV-HCV
Condition: HIV-HCV
Study type: Interventional
Phase: Phase 2

Summary: 
      Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated
      180 million people infected worldwide. In the United States an estimated 4.1 million people
      are infected and HCV is the principal cause of death from liver disease and leading
      indication for liver transplantation. Within HIV/HCV co-infected patients, liver disease due
      to Hepatitis C progresses even more rapidly. While combination of ribavirin (RBV) and
      pegylated interferon (PEG) in combination with boceprevir/telaprevir is the currently
      recommended therapy for chronic HCV infection and has superior cure rates compared to PEG+RBV
      alone in HCV monoinfected patients, treatment is still associated with a high incidence of
      adverse events (AEs), discontinuations and poor cure rates in several populations. Within the
      HIV/HCV co-infected population treatment for HCV remains complicated given drug interactions
      between anti-retrovirals and HCV protease inhibitors, in addition to the extensive
      side-effects due to PEG +RBV alone. Recent studies have demonstrated that the use of a
      combination of anti-virals which target HCV without interferon (IFN) can cure HCV, without
      additional toxicities. These novel therapies that do not rely on an IFN backbone may
      additionally enhance cure rates in HIV/HCV co-infected, a population which has historically
      been difficult to cure.

      The findings from this study will aid in the understanding of antiviral and host responses
      and determinants of response to an IFN free regimen in HIV/HCV co-infected patients.
    

Detailed description: 
      Chronic hepatitis C virus (HCV) infection is a major public health problem with an estimated
      180 million people infected worldwide. In the United States an estimated 4.1 million people
      are infected and HCV is the principal cause of death from liver disease and leading
      indication for liver transplantation. Within HIV/HCV co-infected patients, liver disease due
      to Hepatitis C progresses even more rapidly. While combination of ribavirin (RBV) and
      pegylated interferon (PEG) in combination with boceprevir/telaprevir is the currently
      recommended therapy for chronic HCV infection and has superior cure rates compared to PEG+RBV
      alone in HCV monoinfected patients, treatment is still associated with a high incidence of
      adverse events (AEs), discontinuations and poor cure rates in several populations. Within the
      HIV/HCV co-infected population treatment for HCV remains complicated given drug interactions
      between anti-retrovirals and HCV protease inhibitors, in addition to the extensive
      side-effects due to PEG +RBV alone. Recent studies have demonstrated that the use of a
      combination of anti-virals which target HCV without interferon (IFN) can cure HCV, without
      additional toxicities. These novel therapies that do not rely on an IFN backbone may
      additionally enhance cure rates in HIV/HCV co-infected, a population which has historically
      been difficult to cure.

      This is an open label study to assess the safety, tolerability and efficacy of two regimens
      for the treatment of HCV, asunaprevir (ASV) 100 mg BID and daclatasvir (DCV) 60 mg daily
      (selective HCV NS3 and NS5A inhibitors respectively) in 10 HIV/HCV genotype 1b co-infected
      treatment-naive and treatment experienced individuals and DCV + ASV + BMS-791325 administered
      as a fixed dose combination (FDC) pill in 20 HIV/HCV GT 1a or 1b coinfected treatment-naive
      and treatment experienced individuals.

      The findings from this study will aid in the understanding of antiviral and host responses
      and determinants of response to an IFN free regimen in HIV/HCV co-infected patients.
    

Intervention name(s): Asunaprevir and Daclatasvir; Asunaprevir and Daclatasvir with BMS-791325
Intervention type(s): Drug; Drug
Intervention description(s): Oral treatment with Asunaprevir 100mg (ASV), twice daily, and Daclatasvir 60mg (DCV), once daily, for 24 weeks in HIV/HCV genotype 1b patients; Oral treatment with Asunaprevir 200mg (ASV), Daclatasvir 30 mg (DCV) and BMS-791325 75 mg in a fixed dose combination pill (FDC), twice daily, for 12 weeks in HIV/HCV genotype 1a or 1b patients
Other intervention name(s): Asunaprevir (ASV) and Daclatasvir (DCV); Asunaprevir (ASV) and Daclatasvir (DCV) and BMS-791325 (Beclabuvir)
Intervention MeSH terms: Asunaprevir
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Coinfection; HCV Genotype 1b; Interferon Free therapy; Liver Biopsy; Virological Response