therapeutic hepatitis b vaccine (mimogen-based) joint entecavir in treating chronic hepatitis b patients

Conditions: Chronic Hepatitis B

Summary: the purpose is to evaluate efficacy and safety of therapeutic hepatitis b virus (hbv) vaccine (mimogen-based)) joint entecavir treatment in chronic hepatitis b patients.

eligible subjects are enrolled and assigned into 2 groups randomly with a 1:1 ratio： 1. 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 ； 2. 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).

Eligibility criteria:
inclusion criteria: 1. aged 18-65 years, male or female; 2. 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); 3. hla-a2 positive; 4. 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; 5. tsh in normal value; 6. afp test result no more than high limit of normal value; 7. take effective contraception for subject with child-bearing potential (including females and female partners of males); 8. understand and sign icf approved by ec; 9. willing to comply with the study procedures and complete the study. exclusion criteria: 1. antibodies of hcv, hdv or hiv is positive; 2. ana titer \> 1:100; 3. decompensated liver disease (such as gullet and pylorus varicose veins, hepatic encephalopathy); 4. 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. 5. have used anti-hbv drug ( interferon, lamivudine, adefovir dipivoxil, entecavir and telbivudine ) and immunomodulator ( thymic peptide, etc ) to the administration of study medication; 6. have allergic diathesis or have suspected allergy to εpa-44; 7. female in pregnancy, lactation or those who plan to pregnancy during the course of the study; 8. 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; 9. have history of organ transplantation (except corneal transplantation and hair transplantation); 10. have participated in any other drug clinical investigations within 3 months; 11. any other factors inappropriate for enroll in the study or study completion in the view of the investigator.

Keywords: therapeutic hbv vaccine chronic hepatitis b hbeag positive hbv-specific cytotoxic t lymphocyte