Augmenting response to entecavir using a temporary peginterferon alpha-2a add-on strategy for the treatment of HBeAg-positive chronic hepatitis B (ARES study) - Long-term follow-up of a peginterferon alpha-2a add-on strategy in chronic hepatitis B patients treated with entecavir
- Conditions
- Chronic hepatitis B1001965410047438
- Registration Number
- NL-OMON39757
- Lead Sponsor
- Stichting Leveronderzoek
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 20
• 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)
• 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
- Not specified
- Primary Outcome Measures
Name Time Method <p>The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss at week 48<br /><br><br /><br>According to amendment 5:<br /><br>1. HBeAg loss and presence of HBV DNA level <200 IU/ml </p><br>
- Secondary Outcome Measures
Name Time Method <p>• ALT normalization<br /><br>• Undetectable HBV DNA (* 60 IU/mL)<br /><br>• HBsAg and HBeAg loss from serum<br /><br>• The emergence of HBV polymerase mutations associated with reduced<br /><br>susceptibility to entecavir<br /><br>• Sustained response defined as the combined presence of HBV DNA level < 200<br /><br>IU/mL and HBeAg loss at week 96<br /><br><br /><br>According to amendment 5:<br /><br>2. HBeAg seroconversion (HBeAg negative & anti-HBe positive)<br /><br>3. Serum HBsAg levels<br /><br>4. HBsAg loss and/or seroconversion<br /><br>5. Reconversion to HBeAg positivity after initial HBeAg loss (sustainability of<br /><br>response)<br /><br>6. HBV DNA negativity (<20IU/ml as measured by PCR)<br /><br>7. Regression of fibrosis and inflammation in liver biopsy<br /><br>8. Liver failure, Hepatocellular carcinoma, liver transplantation, death<br /><br>9. IL28B and other genetic variations in relation to points 1-8.</p><br>