The purpose is to evaluate efficacy and safety of therapeutic Hepatitis B Virus(HBV) vaccine (mimogen-based) treatment in chronic hepatitis B patients and to explore the most effective dosage and provide the rational for optimal dosing schedule.
First stage(0-76 weeks): Eligible subjects are enrolled and assigned to 3 groups randomly in a 1:1:1 ratio: 1. εPA-44 600μg group:Subcutaneous inject εPA-44 600μg at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28. 2. εPA-44 900μg group:Subcutaneous inject εPA-44 900μg at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28. 3. Placebo control group:Subcutaneous inject empty liposome at week 0, 4, 8, 12, 20, 28;Polyene Phosphatidylcholine Capsules will be taken orally beginning in week 28. The study cycle consists of screening and enrollment period (week -6-0), treatment period (week 0-28) and follow-up period (week 28-76). Second stage(76-144 weeks): In this follow-up stage the trial is open designed, and all the subjects completed the first stage study(0-76 weeks): 1. Subjects with no virological response and no serological response in the first stage , and refuse to continue the this follow-up study, will be provided domestic Adefovir Dipivoxil for one year freely; 2. Subjects with virological response but no serological response/with serological response but no virological response/neither virological nor serological response in the first stage, and be willing to continue the this follow-up study, will be treated by εPA-44 900 μg; 3. Subjects with both virological and serological response, will be followed-up to 144 weeks with no Adefovir Dipivoxil or εPA-44 900 μg treatment. The definition of response is defined as below: 1. Virological response: HBV DNA\<2.93×10∧3IU/ml at 76 weeks; 2. Serological response: serological conversion of HBeAg at 76 weeks.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
360
The PLA Beijing Military General Hospital
Beijing, Beijing Municipality, China
The 2nd Affiliated Hosptial of Harbin Medical University
Harbin, Heilongjiang, China
Renmin Hosptial of Wuhan University
Percentage of Participants With HBeAg Seroconversion at Endpoint .
Primary endpoint data were summarised under "End of Study",using the last available post-baseline observation(Last Observation Carried Forward,LOCF)
Time frame: Endpoint(LOCF), up to 76 Weeks
Percentage of Participants With HBeAg Seroconversion at Weeks 12, 28, 32, 40, 52, 64, 76
HBeAg seroconversion=HBeAg loss and presence of hepatitis B e antibody (HBeAb). HBeAg is a hepatitis B viral protein and is an indicator of active viral replication
Time frame: serology response at week 12, 28, 32, 40, 52, 64, 76
The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 1 Log Scale;
Time frame: week 12, 28, 32, 40, 52, 64, 76
Percentage of Participants With Alanine Aminotransferase (ALT) Normalization at Weeks 12,28,32,40,52,64,76
Time frame: week 12, 28, 32, 40, 52, 64, 76
The Proportion of Patients With Both Negative HBeAg and HBeAb;
Time frame: at week 12, 28, 32, 40, 52, 64, 76.
The Proportion of Patients With Positive Anti-HBe
Time frame: at week 12, 28, 32, 40, 52, 64, 76.
Change From Baseline by Visit for HBeAg Titer
Measuring the change in value of each visit viewpoints HBeAg titers decreased compared with baseline values
Time frame: at week 12, 28, 32, 40, 52, 64, 76.
The Proportion of Patients With Serum HBV DNA Load Decrease Equal or Greater Than 2 Log Scale;
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Wuhan, Hubei, China
The Second Xiangya Hospital of Central South University
Changsha, Hunan, China
The Third Xiangya Hospital of Central South University
Changsha, Hunan, China
Xiangya Hospital Central South University
Changsha, Hunan, China
81th Hospital of PLA
Nanjing, Jiangsu, China
Jilin University First Hospital
Changchun, Jilin, China
TangDu Hospital
XiAn, Shanxi, China
The First Affiliated Hospital of Xi'An JiaoTong University
Xi’an, Shanxi, China
...and 5 more locations
Time frame: week 12, 28, 32, 40, 52, 64, 76
The Proportion of Patients With Serum HBV DNA Level < 29300 IU / ml;
Time frame: week 12, 28, 32, 40, 52, 64, 76
Change From Baseline by Visit for Serum HBV DNA
Measuring the change in value of each visit viewpoints HBV DNA titers decreased compared with baseline values
Time frame: week 12, 28, 32, 40, 52, 64, 76