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

NCT ID: NCT00877760

Last Updated: 2014-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2013-07-31

Brief 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

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

pegylated interferon a-2a

Intervention Type: DRUG

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

Entecavir

Intervention Type: DRUG

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

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.

Group Type: ACTIVE_COMPARATOR

Entecavir

Intervention Type: DRUG

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

Interventions

pegylated interferon a-2a

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

Intervention Type: DRUG

Entecavir

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

Intervention Type: DRUG

Other Intervention Names

Pegasys; Baraclude

Eligibility 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Liver Research

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Harry Janssen, Prof. dr.

Role: PRINCIPAL_INVESTIGATOR

Foundation for Liver Research (SLO) and Erasmus Medical Center

Locations

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 (Türkiye)

Yuksek Ihsitas Hospital, Dept. Gastroenterology

Ankara, , Turkey (Türkiye)

Cerrahpasa Medical Faculty

Istanbul, , Turkey (Türkiye)

Countries

China; Netherlands; Poland; Romania; Turkey (Türkiye)

References

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.

Reference Type: DERIVED

PMID: 35941076 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30689258 (View on PubMed)

Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.

Reference Type: DERIVED

PMID: 35599306 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25348661 (View on PubMed)

Other Identifiers

HBV 09-01

Identifier Type: -

Identifier Source: org_study_id