Therapeutic Hepatitis B Vaccine (Synthesized Peptide) in Treating Chronic Hepatitis B Patients

• Primary efficacy assessment is the proportion of patients about HBeAg / anti-HBe seroconversion at the end of the follow-up period. [ Time Frame: week 76, week 144 ] [ Designated as safety issue: Yes ]
  First stage: the primary assessment is at week 76, and in second stage is at week 144.
  
  

• Secondary efficacy parameters include serology response at week 12, 28, 32, 40, 52, 64,76, 95,108, 120, 144. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76, 95,108, 120, 144 ] [ Designated as safety issue: Yes ]
  1. The proportion of patients about HBeAg / anti-HBe Serological conversion;
  2. The proportion of patients that HBeAg is negative, but anti-HBe is still negative;
  3. The proportion of patients that anti-HBe is positive;
  4. Change of HBeAg titer.
  
  
• Virological response at each observation time point at week 12, 28, 32, 40, 52, 64, 76. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ] [ Designated as safety issue: Yes ]
  1. The proportion of patients with serum HBV DNA load decrease epual or greater than 1 log scale;
  2. The proportion of patients with serum HBV DNA load decrease epual or greater than 2 log scales;
  3. The proportion of patients with serum HBV DNA level < 2.93 × 104 IU / ml;
  4. Decreased amount of serum HBV DNA compared with the baseline value.
  
  
• Biochemistry response at every observation point. [ Time Frame: week 12, 28, 32, 40, 52, 64, 76 ] [ Designated as safety issue: Yes ]
  1. The proportion of patients with ALT reyurned to normal;
  2. The chang of ALT at every observation point.
  
  
• Virological response at each observation time point at week 95, 108, 120, 144. [ Time Frame: Week 95, 108, 120, 144 ] [ Designated as safety issue: Yes ]
  1. The proportion of patients with serum HBV DNA level unable to be detected or lower than limit;
  2. Decreased amount of serum HBV DNA compared with the baseline value;
  3. The proportion of patients with serum HBV DNA decrease equal or greater 2 log scales or level < 2.93 × 104 IU / ml.
  
  

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):

According to this follow-up stage, open designed, the subjects completed the first stage study(0-76 weeks):

1. If no virological response and no serological response, and refuse to continue the follow-up study, will be provided domestic Adefovir Dipivoxil for one year freely;
2. If have virological response but no serological response/have serological response but no virological response/neither virological nor serological response, and be willing to continue the follow-up study, will be treated by εPA-44 900 μg；
3. If have both virological and serological response, will be observed to 144 weeks.

The definition of response as below:

1. Virological response: HBV DNA＜2.93×103IU/ml at 76 weeks;
2. Serological response: HBeAg appears to serological conversion at 76 weeks.