Phase 2 Trial of Therapeutic Hepatitis B Vaccine (Mimogen-based) for Chronic Hepatitis B
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: εPA-44; Placebo
Intervention description: subcutaneously injection of εPA-44 at week 0, 4, 8, 12, 20, 28.; subcutaneously injection of Placebo at week 0, 4, 8, 12, 20, 28.
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 360.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Chronic Hepatitis B; HBeAg positive; Therapeutic HBV Vaccine; HBV-specific Cytotoxic T Lymphocyte

Summary:

      The purpose is to evaluate efficacy and safety of therapeutic Hepatitis B Virus（HBV） vaccine
      (mimogen-based) treatment in chronic hepatitis B patients and to explore the most effective
      dosage and provide the rational for optimal dosing schedule.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Aged 18-65 years, male or female

          2. Conforms 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), and HBV-DNA more than 100000 copies/ml;HBeAg (+),HBsAb(-); Alanine
             aminotransferase（ALT） within 2 to 10 times of ULN (upper limit of normal)

          3. HLA-A2 positive

          4. Compensatory liver disease having following hematological and biochemical
             indicators:WBC≥3.5E+9/L; ANC≥1.5E+9/L; PLT≥80E+9/L; Hb≥110g/L; TBil≤1.5ULN; ALB ≥
             lower limit of normal value; BUN (Urea)≤upper limit of normal value; Cr≤upper limit of
             normal value; prothrombin time(PT) elongation≤3 sec; Activated partial thromboplastin
             time（APTT） within normal value; Fasting blood glucose≤7.0mmol/L

          5. TSH within normal value

          6. AFP ≤20ng/ml

          7. Uses effective contraception for subject with child-bearing potential (including
             females and female partners of males)

          8. Understands and signs ICF approved by EC

          9. Willing to comply with the study procedures and complete the study

        Exclusion Criteria:

          1. Antibody of HAV IgM, HCV, HDV IgM or HEV IgM is positive

          2. Antibody of CMV IgM, EBV IgM or HIV is positive

          3. Antinuclear antibody titer>1:160

          4. Hepatocarcinoma, suspected hepatocarcinoma or hepatic cirrhosis

          5. Has any of the following illnesses or has a severe disease inappropriate for
             participation in the study based on the investigator's judgment, such as:
             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:
             bronchiectasis, 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 or metal illness history,etc.

          6. Has used anti-HBV drug (Interferon, Lamivudine, Adefovir Dipivoxil, Entecavir and
             Telbivudine) and immunomodulator (Thymic peptide,etc ) 6 months prior to the
             administration of study medication

          7. Has participated in any other drug clinical investigations within the past 3 months

          8. Has allergy habitus or has suspected allergy to study drug

          9. Female who is in pregnancy, in lactation or planning to become pregnant during the
             course of the study

         10. Has a 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

         11. Has a history of organ transplant (except external corneal transplantation and hair
             transplantation)

         12. Any other factors inappropriate for enrollment in the study or study completion in the
             view of the investigator