REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection
Condition: Chronic HBV Infection (HBeAg Negative)
MeSH terms: Infections; Communicable Diseases; Hepatitis B; Coinfection; Hepatitis D; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      REP 2139-Ca is nucleic acid polymer. Nucleic acid polymers have been previously shown to
      clear serum hepatitis B virus surface antigen (HBsAg) both preclinically (in duck HBV
      infected ducks) and in human patients and to act synergistically with immunotherapeutic
      agents such as pegylated interferon-alpha 2a or thymosin alpha-1 to restore host
      immunological control of HBV infection.

      HBsAg is an essential component of the hepatitis D virus (HDV), therefore the direct action
      of REP 2139-Ca in removing serum HBsAg and its synergistic effect with pegylated
      interferon-alpha 2a is expected to have a significant antiviral effect against HDV infection.

      This study will examine the safety and efficacy of REP 2139-Ca therapy when used in
      combination with pegylated interferon alpha-2a in patients with HBV / HDV co-infection.

      The primary hypothesis to be tested is that this combined dosing regimen is safe and well
      tolerated in patients with HBV / HDV co-infection which will be assessed by examining the
      number of patients with adverse events (including reported symptoms and laboratory
      abnormalities).

      The secondary hypothesis to be tested is that this combined dosing regimen will have an
      antiviral effect against HBV / HDV co-infection in these patients which will be assessed by
      examining the following outcomes:

        1. The number of patients with reductions in serum HBsAg.

        2. The number of patients with reductions in serum HDAg and HDV RNA

        3. The number of patients that experience a sustained antiviral response after treatment is
           stopped (reductions in serum HBV DNA and HDV RNA).

      The secondary hypothesis to be tested is that this combination approach can have an effective
    

Detailed description: 
      Nucleic acid polymers (NAPs) utilize the sequence independent properties of phosphorothioated
      oligonucleotides to target apolipoprotein interactions involved in the formation of HBV
      subviral particles (SVPs) which are comprised mainly of the hepatitis B surface antigen
      protein (HBsAg). The effect of NAPs is to block the formation of SVPs inside infected
      hepatocytes which prevents their secretion. As SVPs account for > 99.99% of HBsAg in the
      blood, NAPs are an effective approach for clearing HBsAg from the serum of HBV infected
      patient.

      Previous clinical trials have demonstrated that treatment with the NAP REP 2139 results in
      the rapid and effective clearance of HBsAg from the blood. This HBsAg removal has the
      immediate effect of unmasking the underlying, pre-existing anti-HBsAg (anti-HBs) response,
      allowing clearance of HBV virus from the blood.

      HBsAg has important immunosuppressive effects in HBV infection which have been shown to block
      both adaptive and innate immune processes. Removal of HBsAg from the blood of patients
      removes this immunosuppressive effect.

      Thus, an important additional effect of removal of HBsAg from the blood is to greatly enhance
      the effect of immunotherapeutic agents like pegylated interferon alpha-2a or thymosin alpha-1
      to stimulate recovery of complete immune control of HBV infection.

      HDV superinfection can only occur in patients with HBV infection because HDV requires the
      HBsAg protein for its assembly. Therefore, it is expected that the removal of serum HBsAg
      (from HBV SVPs) and unmasking of the anticipated, pre-existing anti-HBsAg response by REP
      2139 will result in the clearance of HBV and HDV from the blood. Furthermore, the enhanced
      effect of immunotherapy in the absence of serum HBsAg has the potential to provide a durable
      control of both HBV and HDV infection that will persist after treatment.
    

Intervention name(s): REP 2139-Ca + Pegasys (TM)
Intervention type(s): Drug
Intervention description(s): 15 weeks of REP 2139-Ca (500mg QW IV) followed by: 15 weeks of REP 2139-Ca (250mg QW IV) + Pegasys(TM) (180 ug QW SC) followed by: 33 weeks of Pegasys(TM) (180 ug QW SC)
Other intervention name(s): Pegasys(TM) = pegylated interferon alpha-2a
Intervention MeSH terms: Interferons; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a; REP 2139
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment