Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B (ARES)

March 27, 2014 updated by: Foundation for Liver Research

Augmenting Response to Entecavir Using a Temporary Peginterferon Alpha-2a add-on Strategy for the Treatment of HBeAg-positive Chronic Hepatitis B

The purpose of this study is to investigate whether it is possible to augment the response of patients with HBeAg-positive chronic hepatitis B to entecavir by using a temporary peginterferon alpha-2a add-on strategy

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

184

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
      • Shanghai, China
        • Ruijin Hospital
      • Shanghai, China
        • Shanghai Public Health Center
      • Shanghai, China
        • Zhong Shan Hospital, Fu Dan University
  • Netherlands
      • Amsterdam, Netherlands
        • Amsterdam Medical Center (AMC)
      • Rotterdam, Netherlands
        • Erasmus Medical Center
  • Poland
      • Bydgoszcz, Poland
        • CMUMU
      • Wroclaw, Poland
        • Medical University, Dept of Infections Diseases
      • Zawiercie, Poland
        • WAMED
  • Romania
      • Bucharest, Romania
        • Fundeni Clinical Institute
      • Bucharest, Romania
        • Nat. Institute of inf. Disease
  • Turkey
      • Ankara, Turkey
        • University of Ankara, Medical School
      • Ankara, Turkey
        • Yuksek Ihsitas Hospital, Dept. Gastroenterology
      • Istanbul, Turkey
        • Cerrahpasa Medical Faculty

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic hepatitis B (HBsAg positive > 6 months)
  • HBeAg positive, anti-HBe negative at screening
  • ALT > 1.3 x ULN within 60 days prior to screening and during screening
  • Liver biopsy performed within 2 years prior to screening or during screening
  • Age > 18 years
  • Written informed consent
  • Adequate contraception for males and females during treatment and follow up; negative pregnancy test (for women of childbearing potential)

Exclusion Criteria:

  • Antiviral therapy against HBV within the previous 6 months
  • Treatment with any investigational drug within 30 days of screening
  • Previous treatment with lamivudine or telbivudine for more than six months
  • Severe hepatitis activity as documented by ALT>10 x ULN
  • History of decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, bleeding gastric or esophageal varices or encephalopathy)
  • Pre-existent neutropenia (neutrophils < 1,500/mm3) or thrombocytopenia (platelets < 90,000/mm3)
  • Co-infection with hepatitis C virus or human immunodeficiency virus (HIV)
  • Other acquired or inherited causes of liver disease (i.e. alcoholic liver disease, obesity induced liver disease, drug related liver disease, auto-immune hepatitis, hemochromatosis, Wilson's disease or alpha-1 antitrypsin deficiency)
  • Alpha fetoprotein > 50 ng/ml
  • Hyper- or hypothyroidism (subjects requiring medication to maintain TSH levels in the normal range are eligible if all other inclusion/exclusion criteria are met)
  • Immune suppressive treatment within the previous 6 months
  • Contra-indications for alpha-interferon therapy like suspected hypersensitivity to interferon or PEG-interferon or any known pre-existing medical condition that could interfere with the patient's participation in and completion of the study.
  • Pregnancy, lactation
  • Other significant medical illness that might interfere with this study: significant pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g. HIV positivity, auto-immune diseases, organ transplants other than cornea and hair transplant)
  • Any medical condition requiring, or likely to require chronic systemic administration of steroids, during the course of the study
  • Substance abuse, such as alcohol (> 80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
  • Any other condition which in the opinion of the principal investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ETV + pegIFN
Patients receive Entecavir in a dosage of 0.5 mg once daily per os from day 0, up to week 48. From week 24 to week 48, they also receive pegylated-interferon a-2a in a dose of 180 μg per week s.c. At week 48, response will be assessed. Responders will continue to take Entecavir until week 72, and quit subsequently. Non-responders at week 48 will continue on Entecavir up to week 96.
Drug: pegylated interferon a-2a
180 μg, once per week s.c. for 24 weeks
Other Names:
  • Pegasys
Drug: Entecavir
0.5 mg once daily per os, either 72 weeks or 96 weeks
Other Names:
  • Baraclude
Active Comparator: ETV
Patients receive Entecavir in a dosage of 0.5 mg once daily per os from day 0, up to week 48. At week 48, response will be assessed. Responders will continue to take Entecavir until week 72, and quit subsequently. Non-responders at week 48 will continue on Entecavir up to week 96.
Drug: Entecavir
0.5 mg once daily per os, either 72 weeks or 96 weeks
Other Names:
  • Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss
Time Frame: week 48
week 48

Secondary Outcome Measures

Outcome Measure
Time Frame
ALT normalization
Time Frame: up to week 96
up to week 96
Undetectable HBV DNA <60 IU/mL
Time Frame: up to week 96
up to week 96
HBsAg and HBeAg loss from serum
Time Frame: up to week 96
up to week 96
The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir
Time Frame: up to week 96
up to week 96
Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss
Time Frame: week 96
week 96

Collaborators and Investigators

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

Sponsor

Foundation for Liver Research

Investigators

  • Principal Investigator: Harry Janssen, Prof. dr., Foundation for Liver Research (SLO) and Erasmus Medical Center

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

August 1, 2009

Primary Completion (Actual)

July 1, 2013

Study Completion (Actual)

July 1, 2013

Study Registration Dates

First Submitted

April 7, 2009

First Submitted That Met QC Criteria

April 7, 2009

First Posted (Estimate)

April 8, 2009

Study Record Updates

Last Update Posted (Estimate)

March 28, 2014

Last Update Submitted That Met QC Criteria

March 27, 2014

Last Verified

March 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HBV 09-01

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.

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