PEG-IFN in HBV Patients With Incomplete Response to NA

Study Overview
=================
Brief Summary
-----------------
Treatment with a nucleoside analogue and subsequent viral decline has shown to partially restore immune hyporesponsiveness in chronic hepatitis B patients. Recent pilot studies investigating whether the effect of lowering viral load with nucleoside analogue therapy prior to the initiation of peginterferon results in higher sustained off-treatment responses showed contradictory findings. The aim of this study is to investigate sustained off-treatment response to peginterferon alfa-2b in chronic HBeAg-positive hepatitis B patients who are pretreated with nucleos(t)ide analogues, thereby lowering viral load

Official Title
-----------------
Lowering Viral Load With Nucleos(t)Ide Analogues Prior to Peginterferon Alfa-2b Treatment to Increase Sustained Response in HBeAg-positive Chronic Hepatitis B - a Pilot Study

Conditions
-----------------
Chronic Hepatitis B

Intervention / Treatment
-----------------
* Drug: Nucleos(t)ide analogue treatment with a peginterferon add-on strategy
* Drug: Nucleos(t)ide analogue treatment


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chronic hepatitis B (HBsAg positive > 6 months) HBeAg positive, anti-HBe negative within one month prior to initiation of peginterferon alfa-2b HBV DNA < 2000 IU/ml during nucleos(t)ide analogue treatment within one month prior to initiation of peginterferon alfa-2b Compensated liver disease Age > 18 years Written informed consent Exclusion Criteria: 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 Peginterferon 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 (>80 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Continuation of any Nucleos(t)ide analogue treatment and add-on of peginterferon for 24 weeks | Drug: Nucleos(t)ide analogue treatment with a peginterferon add-on strategy<br>* peginterferon 1.5 microgram/kg once a week Treatment with one of the approved nucleos(t)ide analogues<br>|
| Active Comparator: 2<br>Continuation of Nucleos(t)ide analogue mono-therapy | Drug: Nucleos(t)ide analogue treatment<br>* Treatment with one of the approved nucleos(t)ide analogues<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained response defined as HBeAg loss and HBV DNA level < 200 IU/mL |  | at week 72 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis B, sustained response, peginterferon, nucleos(t)ide analogues