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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01326546
• Other study ID #: 71006.04
• Status: Completed
• Phase: Phase 2
• Start date: June 2010
• Est. completion date: January 2014

Study information

• Verified date: March 2019
• Source: Chongqing Jiachen Biotechnology Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 378
• Est. completion date: January 2014
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ePA-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.

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Biological:
• Therapeutic HBV vaccine
Inject ePA-44 900µg at week 0, 3, 6, 9, 12, 15, 18, 21, 24, 28, 32, 36, 40, 44, 48.

Drug:
• entecavir
0.5mg,per day,oral intake.

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

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Chongqing Jiachen Biotechnology Ltd.	Third Military Medical University

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Serological Response	Serological response at every observation time: serological conversion rate of HBeAg, negative conversion rate of HBeAg, and change of HBeAg.	96 weeks
Secondary	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
Secondary	Biochemistry Response	Biochemistry response at every observation time, mean the ALT level reduce to normal.	96 weeks
Secondary	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