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

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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Biological: Therapeutic HBV vaccine; Drug: entecavir; Other: placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 378
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • 302 Militray Hosptial of China
  • ChongQing, China
    • Southwest Hospital
  • Anhui
    • Hefei, Anhui, China
      • The First Affiliated of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Beijing YouAn Hosptial,Capital Medical University
  • Guangdong
    • Shenzhen, Guangdong, China
      • The Third People's Hosptial of Shenzhen
  • Hubei
    • WuHan, Hubei, China
      • Renmin hosptial of Wuhan University
  • Hunan
    • ChangSha, Hunan, China
      • Xiangya Hospital Central South University
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
  • Jiangsu
    • NanJing, Jiangsu, China
      • 81th Hospital of PLA
    • NanJing, Jiangsu, China
      • Jiangsu Province Hospital
    • Nanjing, Jiangsu, China
      • The Second Hospital of Nanjing
  • Shanxi
    • XiAn, Shanxi, China
      • Tangdu Hospital
  • Yunnan
    • Kunming, Yunnan, China
      • First Affiliated Hospital of Kunming Medical University
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • The First Affiliated Hospital of Zhejiang University
    • WenZhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Biological: Therapeutic HBV vaccine; Inject εPA-44 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.; Other Names: εPA-44; Drug: entecavir; 0.5mg,per day,oral intake.; Other Names: Baraclude
Placebo Comparator: 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.	Drug: entecavir; 0.5mg,per day,oral intake.; Other Names: Baraclude; Other: placebo; Inject placebo 900μg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.; Other Names: empty liposome

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HBeAg Seroconversion at Week 48	Primary endpoint data were summarised under "End of Study",using the last available post-baseline observation(Last Observation Carried Forward,LOCF)	48 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serological Response	Serological response at every observation time: serological conversion rate of HBeAg, negative conversion rate of HBeAg, and change of HBeAg.	96 weeks
Virological Response	Virological response at every observation time: the proportion of patients with serum HBV DNA level reduction to undetectable level, decreased amount of serum HBV DNA compared with the baseline value, and HBV DNA load decrease 2 log scales or HBV DNA level <1.72×104 IU/ml.	96 weeks
Biochemistry Response	Biochemistry response at every observation time, mean the ALT level reduce to normal.	96 weeks
Histological Response	Histological response at week 72, mean histological score limited reduce 2 (reduced score 2-5), and no fiber deterioration compare with before treatment.	72 weeks

Collaborators and Investigators

• Sponsor: Chongqing Jiachen Biotechnology Ltd.
• Collaborators: Third Military Medical University
• Investigators: Principal Investigator: LanJuan Li, Ph.D., Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2010
• Primary Completion (Actual): January 1, 2014
• Study Completion (Actual): January 1, 2014

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: March 30, 2011
• First Posted (Estimate): March 31, 2011

Study Record Updates

• Last Update Posted (Actual): June 26, 2019
• Last Update Submitted That Met QC Criteria: March 31, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Chronic Hepatitis B; HBeAg positive; Therapeutic HBV Vaccine; HBV-specific Cytotoxic T Lymphocyte
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Anti-Infective Agents; Antiviral Agents; Entecavir
• Other Study ID Numbers: 71006.04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED