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

NCT ID: NCT01326546

Last Updated: 2019-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 378 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-06-30
• Study Completion Date: 2014-01-31

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).

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Therapeutic HBV vaccine+Entecavir

Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 and Oral intake entecavir 0.5mg per day.

Group Type: EXPERIMENTAL

Therapeutic HBV vaccine

Intervention Type: BIOLOGICAL

Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.

entecavir

Intervention Type: DRUG

0.5mg,per day,oral intake.

placebo+Entecavir

Placebo comparator: Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48 and Oral intake entecavir 0.5mg per day.

Group Type: PLACEBO_COMPARATOR

entecavir

Intervention Type: DRUG

0.5mg,per day,oral intake.

placebo

Intervention Type: OTHER

Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.

Interventions

Therapeutic HBV vaccine

Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.

Intervention Type: BIOLOGICAL

entecavir

0.5mg,per day,oral intake.

Intervention Type: DRUG

placebo

Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.

Intervention Type: OTHER

Other Intervention Names

εPA-44; Baraclude; empty liposome

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Third Military Medical University

OTHER

Sponsor Role: collaborator

Chongqing Jiachen Biotechnology Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

LanJuan Li, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Zhejiang University

Locations

The First Affiliated of Anhui Medical University

Hefei, Anhui, China

Beijing Youan Hosptial,Capital Medical University

Beijing, Beijing Municipality, China

The Third People's Hosptial of Shenzhen

Shenzhen, Guangdong, China

Renmin Hosptial of Wuhan University

Wuhan, Hubei, China

The Second Xiangya Hospital of Central South University

Changsha, Hunan, China

Xiangya Hospital Central South University

Changsha, Hunan, China

81th Hospital of PLA

Nanjing, Jiangsu, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

The Second Hospital of Nanjing

Nanjing, Jiangsu, China

TangDu Hospital

XiAn, Shanxi, China

First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, China

The First Affiliated Hospital of Zhejiang University

Hangzhou, Zhejiang, China

The First Affiliated Hospital of Wenzhou Medical University

Wenzhou, Zhejiang, China

302 Militray Hosptial of China

Beijing, , China

Southwest Hospital

Chongqing, , China

Countries

China

Other Identifiers

71006.04

Identifier Type: -

Identifier Source: org_study_id