Clinical trial NCT01326546: Therapeutic Hepatitis B Vaccine (Mimogen-based) Joint Entecavir in Treating Chronic Hepatitis B Patients
Official title: A Randomized, Double-blind, Multicenter Phase II Clinical Trial to Evaluate the Efficacy and Safety of Therapeutic Hepatitis B Vaccine (Mimogen-based) Joint Entecavir in Treating HBeAg Positive Chronic Hepatitis B Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis B
Keywords: Therapeutic HBV Vaccine
Chronic Hepatitis B
HBeAg positive
HBV-specific Cytotoxic T Lymphocyte
Lead sponsor: Chongqing Jiachen Biotechnology Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Third Military Medical University
First posted: 2011-03-31
Enrollment: 378
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed description: 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.

Primary outcomes:
measure: Percentage of Participants With HBeAg Seroconversion at Week 48
timeFrame: 48 weeks
Secondary outcomes:
measure: Serological Response
timeFrame: 96 weeks
measure: Virological Response
timeFrame: 96 weeks
measure: Biochemistry Response
timeFrame: 96 weeks
measure: Histological Response
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated of Anhui Medical University
state: Anhui
city: Beijing
country: China
facility: Beijing Youan Hosptial,Capital Medical University
state: Beijing
city: Shenzhen
country: China
facility: The Third People's Hosptial of Shenzhen
state: Guangdong
city: WuHan
country: China
facility: Renmin Hosptial of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: ChangSha
country: China
facility: Xiangya Hospital Central South University
state: Hunan
city: NanJing
country: China
facility: 81th Hospital of PLA
state: Jiangsu
city: NanJing
country: China
facility: Jiangsu Province Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: XiAn
country: China
facility: TangDu Hospital
state: Shanxi
city: Kunming
country: China
facility: First Affiliated Hospital of Kunming Medical University
state: Yunnan
city: Hangzhou
country: China
facility: The First Affiliated Hospital of Zhejiang University
state: Zhejiang
city: WenZhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: 302 Militray Hosptial of China
city: ChongQing
country: China
facility: Southwest Hospital
Study officials:
affiliation: Zhejiang University
name: LanJuan Li, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: