Study of Therapeutic Vaccination With Intensified Schedule Plus Pegasys Dual Therapy on Chronic Hepatitis B Infection

A randomized, Open label, Single center, Prospective study to compare efficacy and safety of Therapeutic Vaccination with Intensified schedule plus Pegylated Interferon dual Therapy on Seroclearance of Hepatitis B virus Surface Antigen in Patients with Complete Virological Response Induced by Entecavir (E + VIP)

Inclusion criteria

• Age between 20 and 75 year-old
• HBsAg-positive for > 6 months apart (medical history can be alternative)
• Currently being treated with entecavir 0.5 mg/day for more than 18 months
• Undetectable HBV DNA in serum (<20IU/mL) and HBeAg-negative or positive for > 1year
• HBsAg titer < 3,000 IU/mL
• ALT<300 IU/L
• Signed written informed consent after being instructed about the objective and procedure of the clinical study

Exclusion criteria

• Patients with decompensated liver cirrhosis, any one of the following ① Serum bilirubin > 3 mg/dL

② Prothrombin time > 6 seconds prolonged or INR >2.3

③ Serum albumin < 2.8 g/dL

④ History of ascites, variceal hemorrhage, or hepatic encephalopathy

⑤ Child-Pugh score ≥7 (Child-Pugh class B or C)

• Patients who have evidence of renal insufficiency defined as serum creatinine>1.5 mg/dL
• Patients with psychological problem including depression
• Patients who have previous/current significant co-morbidities including congestive heart failure, chronic kidney disease, hematologic disease and malignancy including hepatocellular carcinoma(patients with malignancy cured 5 years before screening can be enrolled)
• Patients with seropositivity for anti-HCV, anti-HDV or anti-HIV
• Patients who have excessive alcohol consumption (> 30 g/day)
• Patients who have evidence of autoimmune hepatitis, hemochromatosis or Wilson's disease
• Pregnant or breast feeding females or plan for pregnancy or no contraception
• Patients with disease may deteriorate with interferon therapy(eg, autoimmune thyroiditis)
• Patients who have an psoriasis
• Patients who have history of antiviral-resistant HBV after previous treatment with oral antiviral agents
• Previous diagnosis with immunodeficiency or concomitant treatment of immune suppressive agent or previous organ transplantation Recipients
• Patients who have a history of hypersensitivity to study drug
• Uncontrollable seizure, convulsion and/or central nervous system disorders
• Patients with severe bone marrow disorder or with history of hypersensitivity to biologic agent such as vaccine.
• Neutrophil count < 1,500/mm3 or platelet count < 75,000/mm3 or hemoglobin < 10 g/dl
• Patients with Pulmonary disease (in case of history of pulmonary disease with complete recovery, enrollment is on investigator's discretion)
• Patients who have a fever ≥ 38 °C at the baseline
• Patients who have a risk of febrile response or systemic reaction
• Patients who the investigator deems inappropriate to participate in this study