Enterovirus 71 Inactivated Vaccine Clinical Trial
Official title:
Evaluating Immunogenicity and Safety Effect on Combined Immune Effect of EV71 Inactivated Vaccine and HepB、MPSV-A、MR、JE-L：A Multi-center Randomized Controlled Trial
Background: To prevent and control the epidemic of HFMD and related diseases caused by EV71
infection, the development of EV71 vaccine has been developed in many countries or regions.
According to the requirements of drug registration approval, we need to evaluate
immunogenicity and safety effect on combined immune effect of EV71 inactivated vaccine and
other vaccines (HepB、MPSV-A、MR、JE-L).
Method: Four experimental groups (HepB:3+EV71, MPSV-A:1+EV71, MR+EV71, JE-L+EV71) were
included in this clinical trail. In addition to the meningococcal vaccine research group, the
other three groups were followed up for the 4 times. The initial blood samples were
collected, and the first dose vaccine was inoculated at the same time. EV71 second doses of
vaccine were inoculated at 30 day, the blood was collected after 30 days of immunization with
second doses. 6 months of safety follow-up was carried out in the whole clinical trial after
vaccination. The meningococcal vaccine research group increased 1 follow-up after the second
dose of MPSV-A vaccine. The index of immunogenicity and safety effect in four experimental
groups need to be evaluated.
Study design and participants The study was conducted in four provinces (Shandong, Shanxi,
Shaanxi and Hunan) of China, which contains Haiyang city, Rushan city, Shimen County, Chen
Cang District, Qishan County, Taigu County and Qi County. 6/8 months children were recruited
in this study, individuals were randomly assigned to experimental group and control group.
Demographic information (age, sex, height and weight) was made and blood samples were
collected for each individual in the same way.
Vaccine inoculation and follow-up
TestⅠ(HepB:3+EV71):
Experimental group - 6 month old HepB third dose and EV71 first dose were inoculated at the
same time, 7 month old EV71 second dose was inoculated, blood samples from the participants
were collected at 8 month old; Control group 1- 6 month old HepB third dose was inoculated
separately, blood samples from the participants were collected after two months; Control
group 2 - 6 month old EV71 first doses was inoculated, 7 month old EV71 second dose was
inoculated, blood samples from the participants were collected at 8 month old.
TestⅡ(MPSV-A:1+EV71):
Experimental group - 6 month old MPSV-A first dose and EV71 first dose were inoculated at the
same time, 7 month old EV71 second dose was inoculated, 9 month old MPSV-A second dose was
inoculated, blood samples from the participants were collected at 10 month old; Control group
1- 6 month old MPSV-A first dose was inoculated separately, 9 month old MPSV-A second dose
was inoculated separately, blood samples from the participants were collected at 10 month
old; Control group 2 - 6 month old EV71 first doses was inoculated, 7 month old EV71 second
dose was inoculated, blood samples from the participants were collected at 10 month old.
TestⅢ (MR+EV71):
Experimental group - 8 month old MR first dose and EV71 first dose were inoculated at the
same time, 9 month old EV71 second dose was inoculated, blood samples from the participants
were collected at 10 month old.
Control group 1- 8 month old MR first dose was inoculated separately, blood samples from the
participants were collected at 10 month old; Control group 2 - 8 month old EV71 first doses
was inoculated, 9 month old EV71 second dose was inoculated, blood samples from the
participants were collected at 10 month old.
TestⅣ(JE-L+EV71):
Experimental group - 8 month old JE-L first dose and EV71 first dose were inoculated at the
same time, 9 month old EV71 second dose was inoculated, blood samples from the participants
were collected at 10 month old.
Control group 1- 8month old JE-L first dose was inoculated separately, blood samples from the
participants were collected at 10 month old; Control group 2 - 8 month old EV71 first doses
was inoculated, 9 month old EV71 second dose was inoculated, blood samples from the
participants were collected at 10 month old.
EV71 vaccine 0.5ml per dose, Wuhan Biological Products Co., Ltd., Wuhan, Hubei Province,
China; 10μg HepB 0.5ml per dose, Wuhan Biological Products Co., Ltd., Wuhan, Hubei Province,
China; 30ug MPSV-A 0.5ml per dose, Wuhan Biological Products Co., Ltd., Wuhan, Hubei
Province, China; MR 0.5ml per dose, Beijiing Biological Products Co., Ltd., Beijing, China;
JE-L 0.5ml per dose, Chengdu Biological Products Co., Ltd., Chengdu,Sichuan Province, China
Immunogenicity end point Detection of serum antibody EV71 vaccine by culture neutralization
test, the definition of positive for neutralizing antibody titers of <1:8 before inoculation,
inoculation after neutralizing antibody titers than 1:8; or before inoculation neutralizing
antibody titer is above 1:8, the titer of neutralizing antibody after vaccination appeared
more than 4 times the growth.
Hepatitis B vaccine seroconversion was defined as Anti-HBs<10mIU/ml before inoculation,
Anti-HBs after inoculation was more than 10mIU/ml.
Leprosy vaccine using measles rubella immunoglobulin ELISA detection test, measles >200U/ml
positive for rubella >20U/ml positive or positive before inoculation; after inoculation,
antibody positive growth is more than 4 times.
Japanese encephalitis vaccine serum samples by using PRNT test before immunization antibody
titer after inoculation was less than 1:5, at 1:10, or after vaccination antibody titer than
before inoculation is no less than 4 times of growth is positive.
Meningococcal vaccine samples A meningococcal bactericidal antibody level in serum by micro
bactericidal antibody test, the antibody titer after inoculation than before inoculation is
no less than 4 times of growth is positive.
Safety assessment Safety assessment Participants were provided with diary cards to record the
occurrence and severity of solicited local reactions at the injection site (pain, induration,
erythema, edema, pruritus) during 7 days after vaccination, solicited systemic reactions
(fever, headache, fatigued, cough, myalgia, asthenia, vertigo, diarrhea), and any unsolicited
adverse during 29 days after vaccination.
Statistical analyses The quantitative index lists the standard deviation, the median, the
maximum and the minimum, and the qualitative index or the grade index list the frequency
distribution table. The antibody titers of immunogenicity index should be represented by
geometric mean, median, maximum and minimum value and 95% confidence interval. The antibody
titer should be analyzed by logarithmic transformation.
A list of the total population, susceptible and non susceptible seroconversion rate and 95%
confidence interval, and calculation (test group and control group) rate difference and 95%
confidence interval, non-inferiority test; the test group and the control group between the
antibody geometric mean (GMT/GMC) compared with the t test after logarithmic transformation
P, with less than 0.05 as there were statistically significant differences in the standard
;