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Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B

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ClinicalTrials.gov Identifier: NCT02726789
Recruitment Status : Completed
First Posted : April 4, 2016
Results First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Replicor Inc.

Brief Summary:
The REP 201 protocol is a small exploratory study assessing the antiviral effects and tolerability of REP 2139-Ca when used with a full course of pegylated interferon (48 weeks) in treatment naive patients or in patients already receiving entecavir and continuing entecavir with treatment.

Condition or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: REP 2139-Ca Drug: pegylated interferon Drug: entecavir Phase 2

Detailed Description:

Chronic hepatitis B is a long term condition caused by infection of the body with the hepatitis B virus (HBV). This infection often results in inflammation or scarring of the liver and can eventually lead to liver cirrhosis and liver failure. These infections are also one of the major causes of the development of hepatocellular carcinoma (liver cancer).

Although some drugs have been approved to treat chronic hepatitis B infections, they do not provide a complete cure except in rare cases (a cure generally means that a person loses the hepatitis B virus from the blood and the liver and develops a durable immunological control of subsequent HBV infection). However, these drugs do significantly decrease the risk of liver damage and liver cancer arising from the presence of a chronic liver infection by slowing or stopping the production of infectious virus. Thus the primary problem associated with currently available drugs is the lack of clearance of the virus from the hepatocytes which necessitates long term treatment with these drugs. There is clearly a need to identify new drugs that can benefit patients with chronic hepatitis B infections. Nucleic acid-based polymers (NAPs) are a new class of broad-spectrum antiviral compounds which act against HBV infection by blocking the release of the surface antigen protein (HBsAg) from infected hepatocytes.

Current interim data analysis from the REP 102 assessing the activity of the NAP REP 9AC' (REP 2139, given as a calcium chelate complex [REP 2139-Ca]) in patients with chronic HBV infection indicates the following:

  1. REP 2139-Ca is generally well tolerated and patients tolerate short term combined treatment (13-26 weeks) of pegylated interferon and / or thymosin alpha
  2. REP 2139-Ca has achieved serum HBsAg reduction or clearance 9 of 9 patients receiving combined therapy.
  3. Appearance of substantial titers of serum anti-HBs occur with the addition of immunotherapy.
  4. After all treatment is withdrawn, 8 / 9 patients achieved HBV DNA < 116 copies / ml (LLOQ of the Roche Cobas platform) and sustained suppression of viremia (HBV DNA < 1000 cpm, HBsAg < 1 IU / ml) for a period of greater than 1 year was observed in four patients.

This exploratory study is designed to examine if REP 2139-Ca can be safely combined with a full course of pegylated interferon in treatment naive patients and in patients with previous and continuing therapy with entecavir and that similar antiviral effects can be observed as in the previous REP 101 and 102 protocols.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Therapeutic Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B
Study Start Date : October 2012
Actual Primary Completion Date : September 2016
Actual Study Completion Date : December 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Experimental
Patients either treatment naive or with HBV DNA controlled with entecavir receive REP 2139-Ca in combination with pegylated interferon. Only patients receiving entecavir at enrollment continue to receive entecavir during treatment in the study.
Drug: REP 2139-Ca
the nucleic acid polymer REP 2139 formulated as a calcium chelate complex

Drug: pegylated interferon
immunotherapy
Other Name: pegylated interferon alpha 2a, Pegasys(R)

Drug: entecavir
local generic entecavir
Other Name: local generic entecavir




Primary Outcome Measures :
  1. Number of Patients Experiencing Treatment Emergent Laboratory Test Abnormalities or Adverse Events. [ Time Frame: 48 weeks (treatment) ]
    To record side effects, symptoms and adverse effects of exposure to REP 2139-Ca when combined pegylated interferon.


Secondary Outcome Measures :
  1. Number of Patients Experiencing Reductions in Serum HBsAg [ Time Frame: 48 weeks (treatment) ]
    To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBsAg.

  2. Number of Patients Experiencing Reductions in Serum HBV DNA [ Time Frame: 48 weeks (treatment) ]
    To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on serum HBV DNA.

  3. Number of Patients Experiencing Serum Anti-HBs > 10 mIU / ml [ Time Frame: 48 weeks (treatment) ]
    To assess antiviral activity of REP 2139-Ca when combined with pegylated interferon on anti-HBsAg antibody titer.



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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age between 18 and 55
  • HBsAg+
  • Anti-HBs negative
  • Patients currently receiving nucleoside based HBV polymerase inhibitors may be included in the study at the discretion of the Principle Investigator.
  • HIV / hepatitis C / hepatitis delta virus negative
  • Fibrosis with compensation (as determined by Fibroscan and liver enzymes)
  • Non cirrhotic
  • No known active cytomegalovirus infection
  • Willingness to utilize adequate contraception while being treated with REP 9AC' and for 6 months following the end of treatment
  • Adequate venous access allowing weekly intravenous therapies and blood tests

Exclusion Criteria:

  • Evidence of cardiovascular disease
  • Autoimmune hepatitis
  • Presence of Wilson's disease
  • Presence of severe NAFLD
  • Evidence of any other co-existent liver disease
  • Anti-nuclear antibody positive
  • Ultrasonograph of hepato-biliary system: positive for cirrhosis of liver
  • A history of ascites, hepatic encephalopathy or variceal hemorrhage
  • Body weight > 100 kg
  • Platelet count < 75,000, polymorphonuclear cell count < 1,500 or hematocrit < 33%
  • alpha feto protein > 100 ng/ml or the presence of a hepatic mass suggestive of hepatocellular carcinoma .
  • Bilirubin > 2.5 mg/dl
  • Creatinine > 1.5 mg/dl
  • Platelet count < 75,000 / cmm
  • Serum albumin < 35 mg/ml
  • Poorly controlled diabetes mellitus
  • Another serious medical disorder
  • A serious psychiatric disorder
  • Uncontrolled hypertension
  • A history of alcohol abuse within the last year
  • The use of illicit drugs within the past two years
  • Inability to provide informed consent
  • Positive pregnancy test
  • Breastfeeding
  • Inability or unwillingness to provide weekly blood samples
  • Poor venous access making IV infusion too difficult

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02726789


Sponsors and Collaborators
Replicor Inc.
Investigators
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Principal Investigator: Mamun Al-Mahtab, MD Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Publications:
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Responsible Party: Replicor Inc.
ClinicalTrials.gov Identifier: NCT02726789     History of Changes
Other Study ID Numbers: REP 201
First Posted: April 4, 2016    Key Record Dates
Results First Posted: May 8, 2019
Last Update Posted: May 8, 2019
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Replicor Inc.:
nucleic acid polymer REP 2139 HBsAg hepatitis B

Additional relevant MeSH terms:
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Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Interferons
Interferon alpha-2
Interferon-alpha
Peginterferon alfa-2a
Entecavir
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs