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CompletedNCT00877760ARESUpdated Mar 28, 2014

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

A Phase 4 interventional study of pegylated interferon a-2a and Entecavir in Chronic Hepatitis B, sponsored by Foundation for Liver Research. Completed at 13 sites in 5 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2014-03-28.

Sponsored by Foundation for Liver Research · Phase 4, Interventional, and Treatment

Phase
Phase 4
Study type
Interventional
Enrollment
184
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

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

02

Conditions studied

  • Chronic Hepatitis B

Keywords

  • Hepatitis B Entecavir pegylated interferon a-2a
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 184 is above the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Foundation for Liver Research is the lead sponsor of 27 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

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
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Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
184 participants (actual)

Study arms

  • 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 · Drug: Entecavir

  • 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

Interventions

  • Drugpegylated interferon a-2a

    180 μg, once per week s.c. for 24 weeks

    Also known as: Pegasys

  • DrugEntecavir

    0.5 mg once daily per os, either 72 weeks or 96 weeks

    Also known as: Baraclude

06

What researchers measure

Primary outcomes

  1. The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss

    Time frame: week 48

Secondary outcomes

  1. ALT normalization

    Time frame: up to week 96

  2. Undetectable HBV DNA <60 IU/mL

    Time frame: up to week 96

  3. HBsAg and HBeAg loss from serum

    Time frame: up to week 96

  4. The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir

    Time frame: up to week 96

  5. Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss

    Time frame: week 96

07

Study locations

13 sites
  • Ruijin Hospital
    Shanghai, China
  • Shanghai Public Health Center
    Shanghai, China
  • Zhong Shan hospital, Fu Dan University
    Shanghai, China
  • Amsterdam Medical Center (AMC)
    Amsterdam, Netherlands
  • Erasmus Medical Center
    Rotterdam, Netherlands
  • CMUMU
    Bydgoszcz, Poland
  • Medical University, Dept of Infections Diseases
    Wroclaw, Poland
  • WAMED
    Zawiercie, Poland
  • Fundeni Clinical Institute
    Bucharest, Romania
  • Nat. Institute of inf. Disease
    Bucharest, Romania
  • University of Ankara, Medical School
    Ankara, Turkey
  • Yuksek Ihsitas Hospital, Dept. Gastroenterology
    Ankara, Turkey
  • Cerrahpasa Medical Faculty
    Istanbul, Turkey
08

References and documents

Publications

  • Brakenhoff SM, de Knegt RJ, van Campenhout MJH, van der Eijk AA, Brouwer WP, van Bommel F, Boonstra A, Hansen BE, Berg T, Janssen HLA, de Man RA, Sonneveld MJ. End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients. J Microbiol Immunol Infect. 2023 Feb;56(1):31-39. doi: 10.1016/j.jmii.2022.06.002. Epub 2022 Jul 2. PubMed 35941076 ↗
  • Liem KS, van Campenhout MJH, Xie Q, Brouwer WP, Chi H, Qi X, Chen L, Tabak F, Hansen BE, Janssen HLA. Low hepatitis B surface antigen and HBV DNA levels predict response to the addition of pegylated interferon to entecavir in hepatitis B e antigen positive chronic hepatitis B. Aliment Pharmacol Ther. 2019 Feb;49(4):448-456. doi: 10.1111/apt.15098. PubMed 30689258 ↗
  • Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27. PubMed 25348661 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 28, 2014, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00877760
Lead sponsor
Foundation for Liver Research
Responsible party
Sponsor
First posted
Apr 8, 2009
Start date
Aug 2009
Primary completion
Jul 2013
Completion
Jul 2013
Last update
Mar 28, 2014

Study contacts

Harry Janssen, Prof. dr.
principal investigator · Foundation for Liver Research (SLO) and Erasmus Medical Center

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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