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

Phase 2

Completed

• Conditions: Chronic Hepatitis B
• Interventions: Biological: Therapeutic HBV vaccine; Drug: entecavir; Other: placebo

• Registration Number: NCT01326546
• Lead Sponsor: Chongqing Jiachen Biotechnology Ltd.

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).

Study Timeline

• Study Start: 2010-06
• Study First Submitted: 2011-03-28
• Study First Submitted QC: 2011-03-30
• Study First Posted: 2011-03-31
• Primary Completion: 2014-01
• Study Completion: 2014-01
• Status Verified: 2019-03
• Results First Submitted: 2019-03-31
• Results First Submitted QC: 2019-03-31
• Last Update Submitted: 2019-03-31
• Results First Posted: 2019-06-26
• Last Update Posted: 2019-06-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 378

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Therapeutic HBV vaccine+Entecavir	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.
placebo+Entecavir	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.
placebo+Entecavir	placebo	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.
Therapeutic HBV vaccine+Entecavir	Therapeutic HBV vaccine	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.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Serological Response	96 weeks	Serological response at every observation time: serological conversion rate of HBeAg, negative conversion rate of HBeAg, and change of HBeAg.
Virological Response	96 weeks	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.
Biochemistry Response	96 weeks	Biochemistry response at every observation time, mean the ALT level reduce to normal.
Histological Response	72 weeks	Histological response at week 72, mean histological score limited reduce 2 (reduced score 2-5), and no fiber deterioration compare with before treatment.

Trial Locations

Locations (15)

The First Affiliated of Anhui Medical University; 🇨🇳 Hefei, Anhui, China

81th Hospital of PLA; 🇨🇳 NanJing, Jiangsu, China

Jiangsu Province Hospital; 🇨🇳 NanJing, Jiangsu, China

The Third People's Hosptial of Shenzhen; 🇨🇳 Shenzhen, Guangdong, China

TangDu Hospital; 🇨🇳 XiAn, Shanxi, China

Beijing Youan Hosptial,Capital Medical University; 🇨🇳 Beijing, Beijing, China

Renmin Hosptial of Wuhan University; 🇨🇳 WuHan, Hubei, China

First Affiliated Hospital of Kunming Medical University; 🇨🇳 Kunming, Yunnan, China

The Second Xiangya Hospital of Central South University; 🇨🇳 Changsha, Hunan, China

302 Militray Hosptial of China; 🇨🇳 Beijing, China

The First Affiliated Hospital of Wenzhou Medical University; 🇨🇳 WenZhou, Zhejiang, China

The Second Hospital of Nanjing; 🇨🇳 Nanjing, Jiangsu, China

Xiangya Hospital Central South University; 🇨🇳 ChangSha, Hunan, China

Southwest Hospital; 🇨🇳 ChongQing, China

The First Affiliated Hospital of Zhejiang University; 🇨🇳 Hangzhou, Zhejiang, China