Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B
Phase 4
Completed
- Conditions
- Chronic Hepatitis B
- Interventions
- Drug: pegylated interferon a-2a
- Registration Number
- NCT00877760
- Lead Sponsor
- Foundation for Liver Research
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 184
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ETV + pegIFN pegylated interferon a-2a 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. ETV + pegIFN Entecavir 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. ETV Entecavir 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.
- Primary Outcome Measures
Name Time Method The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss week 48
- Secondary Outcome Measures
Name Time Method Undetectable HBV DNA <60 IU/mL up to week 96 The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir up to week 96 HBsAg and HBeAg loss from serum up to week 96 ALT normalization up to week 96 Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss week 96
Trial Locations
- Locations (13)
Nat. Institute of inf. Disease
🇷🇴Bucharest, Romania
CMUMU
🇵🇱Bydgoszcz, Poland
WAMED
🇵🇱Zawiercie, Poland
Shanghai Public Health Center
🇨🇳Shanghai, China
Amsterdam Medical Center (AMC)
🇳🇱Amsterdam, Netherlands
Zhong Shan hospital, Fu Dan University
🇨🇳Shanghai, China
Ruijin Hospital
🇨🇳Shanghai, China
Erasmus Medical Center
🇳🇱Rotterdam, Netherlands
University of Ankara, Medical School
🇹🇷Ankara, Turkey
Medical University, Dept of Infections Diseases
🇵🇱Wroclaw, Poland
Cerrahpasa Medical Faculty
🇹🇷Istanbul, Turkey
Fundeni Clinical Institute
🇷🇴Bucharest, Romania
Yuksek Ihsitas Hospital, Dept. Gastroenterology
🇹🇷Ankara, Turkey