A randomized controlled phase IIb trial of antigen-antibody immunogenic complex therapeutic vaccine in chronic hepatitis B patients.
BACKGROUND
The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed.


RESULTS
Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8% (17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05).


CONCLUSIONS
Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated.


BACKGROUND
ChiCTR.org ChiCTR-TRC-00000022.
Xu
Dao-Zhen
DZ
Ditan Hospital, Beijing, China.
Zhao
Kai
K
Guo
Li-Min
LM
Li
Lan-Juan
LJ
Xie
Qing
Q
Ren
Hong
H
Zhang
Ji-Ming
JM
Xu
Min
M
Wang
Hui-Fen
HF
Huang
Wen-Xiang
WX
Wang
Wen-Xiang
WX
Bai
Xue-Fan
XF
Niu
Jun-Qi
JQ
Liu
Pei
P
Chen
Xin-Yue
XY
Shen
Xin-Liang
XL
Yuan
Zheng-Hong
ZH
Wang
Xuan-Yi
XY
Wen
Yu-Mei
YM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000936:Antigen-Antibody Complex / Q000627:therapeutic use; D004279:DNA, Viral / Q000378:metabolism; D017325:Hepatitis B Vaccines / Q000276:immunology / Q000627:therapeutic use*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007700:Kinetics; D008875:Middle Aged
D000936:Antigen-Antibody Complex; D004279:DNA, Viral; D017325:Hepatitis B Vaccines; C532376:YIC vaccine