Clinical trial NCT00877760: Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B
Official title: Augmenting Response to Entecavir Using a Temporary Peginterferon Alpha-2a add-on Strategy for the Treatment of HBeAg-positive Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: Hepatitis B Entecavir pegylated interferon a-2a
Lead sponsor: Foundation for Liver Research
Sponsor class: OTHER
First posted: 2009-04-08
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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
* 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

Primary outcomes:
measure: The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss
timeFrame: week 48
Secondary outcomes:
measure: ALT normalization
timeFrame: up to week 96
measure: Undetectable HBV DNA <60 IU/mL
timeFrame: up to week 96
measure: HBsAg and HBeAg loss from serum
timeFrame: up to week 96
measure: The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir
timeFrame: up to week 96
measure: Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss
timeFrame: week 96
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Ruijin Hospital
city: Shanghai
country: China
facility: Shanghai Public Health Center
city: Shanghai
country: China
facility: Zhong Shan hospital, Fu Dan University
city: Amsterdam
country: Netherlands
facility: Amsterdam Medical Center (AMC)
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
city: Bydgoszcz
country: Poland
facility: CMUMU
city: Wroclaw
country: Poland
facility: Medical University, Dept of Infections Diseases
city: Zawiercie
country: Poland
facility: WAMED
city: Bucharest
country: Romania
facility: Fundeni Clinical Institute
city: Bucharest
country: Romania
facility: Nat. Institute of inf. Disease
city: Ankara
country: Turkey
facility: University of Ankara, Medical School
city: Ankara
country: Turkey
facility: Yuksek Ihsitas Hospital, Dept. Gastroenterology
city: Istanbul
country: Turkey
facility: Cerrahpasa Medical Faculty
Study officials:
affiliation: Foundation for Liver Research (SLO) and Erasmus Medical Center
name: Harry Janssen, Prof. dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.