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

NCT00877760 | Completed Phase 4

• 1 other identifier: HBV 09-01
• Study Type: interventional
• Target: 184
• Locations: 5 countries
• Sites: 13

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

Keywords

Hepatitis B Entecavir pegylated interferon a-2a

Outcome Measures

Primary Outcomes (1)

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

  week 48

Secondary Outcomes (5)

• ALT normalization

  up to week 96

• Undetectable HBV DNA <60 IU/mL

  up to week 96

• HBsAg and HBeAg loss from serum

  up to week 96

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

  up to week 96

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

  week 96

Study Arms (2)

ETV + pegIFN

EXPERIMENTAL

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

ETV

ACTIVE COMPARATOR

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

pegylated interferon a-2a DRUG

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

Also known as: Pegasys

ETV + pegIFN

Entecavir DRUG

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

Also known as: Baraclude

ETV; ETV + pegIFN

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Foundation for Liver Research: lead

Study Sites (13)

Ruijin Hospital

Shanghai, China

Location

Shanghai Public Health Center

Shanghai, China

Location

Zhong Shan hospital, Fu Dan University

Shanghai, China

Location

Amsterdam Medical Center (AMC)

Amsterdam, Netherlands

Location

Erasmus Medical Center

Rotterdam, Netherlands

Location

CMUMU

Bydgoszcz, Poland

Location

Medical University, Dept of Infections Diseases

Wroclaw, Poland

Location

WAMED

Zawiercie, Poland

Location

Fundeni Clinical Institute

Bucharest, Romania

Location

Nat. Institute of inf. Disease

Bucharest, Romania

Location

University of Ankara, Medical School

Ankara, Turkey (Türkiye)

Location

Yuksek Ihsitas Hospital, Dept. Gastroenterology

Ankara, Turkey (Türkiye)

Location

Cerrahpasa Medical Faculty

Istanbul, Turkey (Türkiye)

Location

Related Publications (4)

• 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.

  PMID: 35941076 DERIVED

• 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.

  PMID: 35599306 DERIVED

• 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.

  PMID: 30689258 DERIVED

• 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.

  PMID: 25348661 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a; entecavir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Harry Janssen, Prof. dr.

  Foundation for Liver Research (SLO) and Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2009
• First Posted: April 8, 2009
• Study Start: August 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: March 28, 2014

Record last verified: 2014-03

Locations

CN (3); RO (2); TU (3); PL (3); NL (2)