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

April 17, 2019 updated by: Replicor Inc.

Therapeutic Safety and Efficacy of Combination Treatment With REP 2139-Ca and Pegasys in Patients With Chronic Hepatitis B

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • pegylated interferon alpha 2a, Pegasys(R)
Drug: entecavir
local generic entecavir
Other Names:
  • local generic entecavir

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
48 weeks (treatment)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
48 weeks (treatment)
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.
48 weeks (treatment)
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.
48 weeks (treatment)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Replicor Inc.

Investigators

  • Principal Investigator: Mamun Al-Mahtab, MD, Bangabandhu Sheikh Mujib Medical University, Dhaka, Bangladesh

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2012

Primary Completion (Actual)

September 1, 2016

Study Completion (Actual)

December 1, 2016

Study Registration Dates

First Submitted

March 18, 2016

First Submitted That Met QC Criteria

March 29, 2016

First Posted (Estimate)

April 4, 2016

Study Record Updates

Last Update Posted (Actual)

May 8, 2019

Last Update Submitted That Met QC Criteria

April 17, 2019

Last Verified

February 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • REP 201

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Hepatitis B, Chronic

Clinical Trials on REP 2139-Ca

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Poland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe