OWERING VIRAL LOAD WITH NUCLEOS(T)IDE ANALOGUES PRIOR TO PEG-INTERFERON ALFA-2B TREATMENT TO INCREASE SUSTAINED RESPONSE IN HBEAG-POSITIVE CHRONIC HEPATITIS B (PADD-STUDY)
- Conditions
- Chronic hepatitis B virus infectionMedDRA version: 9.1Level: LLTClassification code 10008910Term: Chronic hepatitis B
- Registration Number
- EUCTR2008-007446-54-NL
- Lead Sponsor
- Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- Not specified
·Chronic hepatitis B (HBsAg positive > 6 months)
·HBeAg positive, anti-HBe negative within one month prior to initiation of peg-interferon alfa-2b
·HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peg-interferon alfa-2b
·Compensated liver disease
·Age > 18 years
·Written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
·Treatment with any investigational drug within 30 days of entry to this protocol
·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 £1,800/mm3) or thrombocytopenia (platelets £90,000/mm3)
·Co-infection with hepatitis C virus, hepatitis D virus or human immunodeficiency virus (HIV)
·Other acquired or inherited causes of liver disease: 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 alfa-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, breast-feeding
·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 (³80 g/day), I.V. drugs and inhaled drugs in the past 2 years.
·Any other condition which in the opinion of the 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 clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: To investigate sustained HBeAg response to peg-interferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load;Secondary Objective: ·Determine the effect of PEG-IFNa on NK cell function and induction HBV-specific immunity in patients with relatively low viral load.<br>·Determine whether NK cell function and HBV-specific T cell response can be predictive for sustained off-treatment effective HBV-specific immunity<br>;Primary end point(s): Primary outcome (response):<br>Sustained response defined as HBV DNA level < 200 IU/ml and HBeAg loss at week 72<br>Secondary outcomes:<br>·Frequency, phenotype and function of NK cells,Treg and DCs.<br>·Determination of HBV-specific T cell response<br>·Determination of HBV and proteins in/on NK cells<br><br>
- Secondary Outcome Measures
Name Time Method