Therapeutic Hepatitis B Vaccine (Mimogen-based) Joint Entecavir in Treating Chronic Hepatitis B Patients

Eligible subjects are enrolled and assigned into 2 groups randomly with a 1:1 ratio：

• Therapeutic HBV vaccine Joint Entecavir group：Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day ；
• Empty liposome Joint Entecavir group：Inject empty liposome at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 + Oral intake entecavir 0.5mg per day.

The study cycle consists of screening and enrollment period (week -4～0), treatment and follow-up period (week 0-96).

Inclusion criteria

• Aged 18-65 years, male or female;
• Conforming to diagnosis standard of chronic hepatitis B according to " 2005 Guideline for Prevention and Treatment of Hepatitis B " , (with positive HBsAg for more than 6 months), never have systemic treatment of anti-HBV viral ,and

• HBV-DNA ≥ 1.72×10^4 IU/ml；
• HBeAg (+), HBeAb (-)；
• ALT within 2 to 10 times of ULN (upper limits of normal);
• HLA-A2 positive;
• Compensatory liver disease having following hematological and biochemical parameters:

• WBC ≥ 3.5×10^9/L;
• ANC ≥ 1.5×10^9/L;
• PLT ≥ 80×10^9/L;
• Hb ≥ 100g/L;
• TBil ≤ 1.5 ULN;
• ALB not lower than low limit of normal value;
• BUN no more than high limit of normal value;
• Cr ≤ 1.5 ULN high limit of normal value;
• PT elongation ≤ 3 sec, APTT in normal value;
• Fasting blood glucose ≤ 7.0mmol/L;
• TSH in normal value;
• AFP test result no more than high limit of normal value;
• Take effective contraception for subject with child-bearing potential (including females and female partners of males);
• Understand and sign ICF approved by EC;
• Willing to comply with the study procedures and complete the study.

Exclusion criteria

• Antibodies of HCV, HDV or HIV is positive;
• ANA titer > 1:100;
• Decompensated liver disease (such as gullet and pylorus varicose veins, hepatic encephalopathy);
• Have the following illness or with severe disease inappropriate to participate in the study in the view of the investigator, in cardiovascular system: instable or significant cardiovascular illness such as angina pectoris, heart attack of myocardial infarction, congestive heart failure, severe hypertension, significant arrhythmia or abnormal ECG etc;

• Respiratory system: bronchiectasia, bronchial asthma, chronic obstructive pulmonary disease, respiratory failure, etc;
• Endocrine, metabolism diseases: diabetes mellitus, uncontrolled thyroid diseases, etc;
• Others: autoimmune disorder, active tuberculosis, malignancies (e.g.: tumor), neuropathic, metal, acute or chronic pancreatitis illness history, etc.
• Have used anti-HBV drug ( Interferon, Lamivudine, Adefovir Dipivoxil, Entecavir and Telbivudine ) and immunomodulator ( Thymic peptide, etc ) to the administration of study medication;
• Have allergic diathesis or have suspected allergy to εPA-44;
• Female in pregnancy, lactation or those who plan to pregnancy during the course of the study;
• Have history of alcohol abuse (Alcohol consumption for more than 5 years, with daily consumption over 40g for males and over 20g for females) and known drug dependence;
• Have history of organ transplantation (except corneal transplantation and hair transplantation);
• Have participated in any other drug clinical investigations within 3 months;
• Any other factors inappropriate for enroll in the study or study completion in the view of the investigator.