Therapeutic Hepatitis B Vaccine (Mimogen-based) Joint Entecavir in Treating Chronic Hepatitis B Patients
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Therapeutic HBV vaccine; entecavir; placebo
Intervention description: Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.; 0.5mg,per day,oral intake.; Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.
Intervention MeSH terms: Entecavir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 378.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Therapeutic HBV Vaccine; Chronic Hepatitis B; HBeAg positive; HBV-specific Cytotoxic T Lymphocyte

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.
    

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.