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

Chronic Hepatitis B Clinical Trial

— ARES  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00877760
• Other study ID #: HBV 09-01
• Status: Completed
• Phase: Phase 4
• First received: April 7, 2009
• Last updated: March 27, 2014
• Start date: August 2009
• Est. completion date: July 2013

Study information

• Verified date: March 2014
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Netherlands: Medical Ethics Review Committee (METC)China: Ethics CommitteePoland: Ethics CommitteePoland: Ministry of HealthRomania: Ethics CommitteeRomania: National Medicines AgencyTurkey: Ethics CommitteeTurkey: Ministry of Health
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 184
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• pegylated interferon a-2a
180 µg, once per week s.c. for 24 weeks
• Entecavir
0.5 mg once daily per os, either 72 weeks or 96 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Liver Research

Countries where clinical trial is conducted

China,  Netherlands,  Poland,  Romania,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss		week 48	No
Secondary	ALT normalization		up to week 96	No
Secondary	Undetectable HBV DNA <60 IU/mL		up to week 96	No
Secondary	HBsAg and HBeAg loss from serum		up to week 96	No
Secondary	The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir		up to week 96	No
Secondary	Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss		week 96	No