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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Foundation for Liver Research
ClinicalTrials.gov Identifier:
NCT00877760
First received: April 7, 2009
Last updated: March 27, 2014
Last verified: March 2014
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis B
Drug: pegylated interferon a-2a
Drug: Entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Augmenting Response to Entecavir Using a Temporary Peginterferon Alpha-2a add-on Strategy for the Treatment of HBeAg-positive Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by Foundation for Liver Research:

Primary Outcome Measures:
  • The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ALT normalization [ Time Frame: up to week 96 ] [ Designated as safety issue: No ]
  • Undetectable HBV DNA <60 IU/mL [ Time Frame: up to week 96 ] [ Designated as safety issue: No ]
  • HBsAg and HBeAg loss from serum [ Time Frame: up to week 96 ] [ Designated as safety issue: No ]
  • The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir [ Time Frame: up to week 96 ] [ Designated as safety issue: No ]
  • Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss [ Time Frame: week 96 ] [ Designated as safety issue: No ]

Enrollment: 184
Study Start Date: August 2009
Study Completion Date: July 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Pegasys
Drug: Entecavir
0.5 mg once daily per os, either 72 weeks or 96 weeks
Other Name: 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 Name: Baraclude

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00877760

Locations
China
Ruijin Hospital
Shanghai, China
Shanghai Public Health Center
Shanghai, China
Zhong Shan hospital, Fu Dan University
Shanghai, China
Netherlands
Amsterdam Medical Center (AMC)
Amsterdam, Netherlands
Erasmus Medical Center
Rotterdam, Netherlands
Poland
CMUMU
Bydgoszcz, Poland
Medical University, Dept of Infections Diseases
Wroclaw, Poland
WAMED
Zawiercie, Poland
Romania
Fundeni Clinical Institute
Bucharest, Romania
Nat. Institute of inf. Disease
Bucharest, Romania
Turkey
University of Ankara, Medical School
Ankara, Turkey
Yuksek Ihsitas Hospital, Dept. Gastroenterology
Ankara, Turkey
Cerrahpasa Medical Faculty
Istanbul, Turkey
Sponsors and Collaborators
Foundation for Liver Research
Investigators
Principal Investigator: Harry Janssen, Prof. dr. Foundation for Liver Research (SLO) and Erasmus Medical Center
  More Information

No publications provided

Responsible Party: Foundation for Liver Research
ClinicalTrials.gov Identifier: NCT00877760     History of Changes
Other Study ID Numbers: HBV 09-01
Study First Received: April 7, 2009
Last Updated: March 27, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Netherlands: Medical Ethics Review Committee (METC)
China: Ethics Committee
Poland: Ethics Committee
Poland: Ministry of Health
Romania: Ethics Committee
Romania: National Medicines Agency
Turkey: Ethics Committee
Turkey: Ministry of Health

Keywords provided by Foundation for Liver Research:
Hepatitis B Entecavir pegylated interferon a-2a

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
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
Interferon-alpha
Interferons
Peginterferon alfa-2a
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents

ClinicalTrials.gov processed this record on August 21, 2014