A Study to Evaluate the Safety and Efficacy of Therapeutic Hepatitis B Vaccine

• Objectives: To explore the appropriate dose of a therapeutic hepatitis B vaccine through the evaluation of safety, tolerability, and efficacy
• Subjects: Chronic hepatitis B carrier with normal ALT range
• Study hypothesis: The immune tolerance break and strong immune responses in the chronic hepatitis B carrier could be achieved with therapeutic hepatitis B vaccine containing novel adjuvant

Inclusion criteria

• Adult between 19 to 60 years of age
• Chronic hepatitis B carriers (HBsAg positive over 6 months)
• HBeAg positive patient, or patient who had lost HBeAg during Antiviral drug treatment
• Antiviral drug treated patient reducing the HBV DNA level below 2000 IU/mL measured by COBAS TaqManM HBV Test (Duration of drug administration should be over 6 months and no limitation on the type of antiviral drug)
• Patient has low ALT than 1.1 fold of upper limit of normal ALT level at screening
• Patient is able to provide written informed consent by oneself or legal representative

Exclusion criteria

• Patient has liver diseases except chronic hepatitis B (i.e. hematochromatosis, alcoholic liver disease, nonalcoholic fatty liver disease, alpha-1 antitrypsin deficiency etc.)
• Patient has one or more test results and symptoms at the screening

• ALT > upper limit of normal level X 1.1
• Total bilirubin > upper limit of normal
• Prothrombin time > Over 3 second than normal
• Serum Albumin < 30 g/L (3 g/dL)
• Patient has history of ascites, yellow jaundice, variceal hemorrhage, hepatic encephalopathy, or liver failure
• Liver FibroScan > F3 (F0: no fibrosis, F1: portal fibrosis, F2: periportal fibrosis, F3: septal fibrosis, F4: cirrhosis)
• Patient has one or more test results at the screening

• Hemoglobin < 9.0 g/dL
• Absolute neutrophil count (ANC) < 1.5 x 109 /L (1500 /mm3)
• Platelet count < 100 x 109 /L (100 x 103 /mm3)
• Serum creatinine > 1.5 mg/dL
• Serum amylase > 2 x ULN and Lipase > 2 x ULN
• Patient has history of Interferon treatment
• Patient is pregnant or breastfeeding or intending to become pregnant during the study
• Patient has active microbial, viral, or fungal infections in need of systemic treatment
• Alpha-fetoprotein (AFP) > 50 ng/mL or Hepatocellular Carcinoma (HCC) patient
• Among the patients treated with immunosuppressive drug within 6 months before screening, suspected case of the declined immunity in the opinion of the investigator
• Patient had long term systemic treatment (more than 14 days consecutively) of high dose (over 20 mg of prednisolone or equivalent dose*) corticosteroid (Decision to participate of patient who had local treatment of corticosteroid is allowed in the opinion of the investigator)

*equivalent to cortisone 125 mg, hydrocortisone 100 mg, prednisone 20 mg, methylprednisolone 16 mg, triamcinolone 16 mg, dexamethasone 3 mg, or betamethasone 2.4 mg

• Patient diagnosed with a malignant tumor within 5 years before screening or relapsed patient (Benign tumor patient is able to participate in this study at the discretion of the investigator)
• Patient has history of organ transplantation
• Patient has serious disease judged by investigator such as heart failure, renal failure, and pancreatitis
• Patient has history of serious heart disease (NYHA Functional Class III or IV heart failure, myocardial infarction within 6 months, treatment required ventricular tachyarrhythmias, or unstable angina etc.)
• Patient has seizure disorder required anticonvulsants treatment
• Uncontrollable diabetic patient (FBS>130mg/dl, HbA1c>7.5%)
• Uncontrollable hypertension patient (SBP≥140mmHg 또는 DBP≥90mmHg)
• HCV, HDV, or HIV patient
• Patient has a plan to participate in other clinical study, or took part in other clinical study within 1 month before enrollment
• Patient has hypersensitivity or anaphylactic reaction for components of investigational product or HBV vaccine
• Patient has continuous drinking (>21 units/week, 1 unit = 10g of pure alcohol) or dependence on alcohol
• Patient concerned about the decline in daily activity or not able to understand the objectives and methods due to the psychiatric problems
• Patient has potential to severe febrile or systemic reaction
• Subject unacceptable in this study under the opinion of the investigator