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REP 2139-Ca / Pegasys™ Combination Therapy in Hepatitis B / Hepatitis D Co-infection
REP2139-Ca/派罗欣联合治疗 B型肝炎/ D型肝炎合并感染
Purpose
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:
The number of patients with reductions in serum HBsAg.
The number of patients with reductions in serum HDAg and HDV RNA
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
Condition Intervention Phase
Hepatitis B With Hepatitis D Superinfection
Drug: REP 2139-Ca + Pegasys (TM)
Phase 2
Estimated Enrollment: 12
Study Start Date: September 2014
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
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.
Locations
Moldova, Republic of
Infectious Clinical Hospital ( n.a. Toma Ciorba) Not yet recruiting
Chisinau, Moldova, Republic of, 2004
Contact: Victor Pantea, MD +373 69 37 11 27 [email protected]
Contact: Valentin Cebotarescu, MD +373 79 50 51 46 [email protected]
Principal Investigator: Victor Pantea, MD
Sponsors and Collaborators
REPLICor Inc.
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发表于 2014-9-13 17:56
