Augmenting Response to Entecavir With Peginterferon a-2a for the Treatment of HBeAg-positive Chronic Hepatitis B

Study Overview
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Brief Summary
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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

Official Title
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Augmenting Response to Entecavir Using a Temporary Peginterferon Alpha-2a add-on Strategy for the Treatment of HBeAg-positive Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: pegylated interferon a-2a
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ETV + pegIFN<br>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. | Drug: pegylated interferon a-2a<br>* 180 μg, once per week s.c. for 24 weeks<br>* Other names: Pegasys;Drug: Entecavir<br>* 0.5 mg once daily per os, either 72 weeks or 96 weeks<br>* Other names: Baraclude;|
| Active Comparator: ETV<br>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. | Drug: Entecavir<br>* 0.5 mg once daily per os, either 72 weeks or 96 weeks<br>* Other names: Baraclude;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The combined presence of HBV DNA level < 200 IU/mL and HBeAg loss |  | week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ALT normalization |  | up to week 96 | 
| Undetectable HBV DNA <60 IU/mL |  | up to week 96 | 
| HBsAg and HBeAg loss from serum |  | up to week 96 | 
| The emergence of HBV polymerase mutations associated with reduced susceptibility to entecavir |  | up to week 96 | 
| Sustained response defined as the combined presence of HBV DNA level < 200 IU/mL and HBeAg loss |  | week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B Entecavir pegylated interferon a-2a