Chronic HBV Infection (HBeAg Negative) Clinical Trial
Official title:
A Study of the Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys™ in Patients With Hepatitis B / Hepatitis D Co-infection
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
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.
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