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
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 1,944
- 试验地点
- 1
- 主要终点
- Antibody titer / concentration to vaccination
研究概览
简要总结
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.
详细描述
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):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 6 Months 至 12 Months（Child）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Inclusion criteria for group Ⅰ（HepB:3+EV71）were as follows:
- •aged ≥ 6 months
- •sign the informed consent form
- •the legal guardians participate in all the planned follow-up and be able to comply with all research procedures
- •the subjects have completed the basic immunization of 2 needle recombinant hepatitis B vaccine, there is no inoculation history of EV71 vaccine, and no history of EV71 infection
- •the last vaccination intervals ≥ 14 days
- •temperature ≤ 37℃
- •Inclusion criteria for group Ⅱ（MPSV-A:1+EV71）were as follows:
- •aged ≥ 6 months
- •sign the informed consent form
- •the legal guardians participate in all the planned follow-up and be able to comply with all research procedures
- •there is no inoculation history of EV71 vaccine, and there is no history of EV71 infection
- •the last vaccination intervals ≥ 14 days
- •temperature ≤ 37℃
- •Inclusion criteria for group Ⅲ（MR+EV71）were as follows:
- •aged ≥ 8 months
- •sign the informed consent form
- •the legal guardians participate in all the planned follow-up and be able to comply with all research procedures
- •there is no inoculation history of EV71 vaccine, and there is no history of EV71 infection
- •the last vaccination intervals ≥ 14 days and the last attenuated live vaccine intervals≥28days
- •temperature ≤ 37℃
- •Inclusion criteria for group Ⅳ（JE-L+EV71）were as follows:
- •aged ≥ 8 months
- •sign the informed consent form
- •the legal guardians participate in all the planned follow-up and be able to comply with all research procedures
- •there is no inoculation history of EV71 vaccine, and there is no history of EV71 infection
- •the last vaccination intervals ≥ 14 days and the last attenuated live vaccine intervals ≥ 28 days
- •temperature ≤ 37℃
排除标准
- •Exclusion criteria for first needle:
- •the history or family history of anaphylaxis, convulsion, epilepsy, encephalopathy and psychosis
- •the history of severe inoculation allergies
- •patients with immunodeficiency and malignant tumors during the treatment period, receiving immunosuppressive therapy (oral steroid) or HIV due to low immunity, or family members have congenital immune disease
- •Nonspecific immunoglobulin was injected within one month
- •temperature≥37.1℃ and infectious diseases
- •the history of thrombocytopenia or other thrombocytopenia with a definite diagnosis
- •respiratory disease, acute infection or chronic disease activity period
- •severe cardiovascular disease, liver and kidney disease, and complications of diabetes
- •infectious, suppurative and allergic dermatosis
- •other conditions that may affect the evaluation of the trail
- •Exclusion criteria for follow-up needle:
- •any serious adverse events that have a causal relationship with the inoculation of the upper dose of the vaccine
- •the abnormality of 4 levels (local, systemic adverse reactions and vital signs) was judged to be related to vaccination
- •other new standards of exclusion criteria for first needle
- •other conditions that may affect the evaluation of the trail
研究组 & 干预措施
Combination inoculation group
GroupⅠ: HepB:3 and EV71 were injected at 6 months old, EV71 second dose was injected at 7 months old GroupⅡ: MPSV-A:1 and EV71 were injected at 6 months old, EV71 second dose was injected at 7 months old, MPSV-A:1 second dose was injected at 9 months old GroupⅢ: MR and EV71 were injected at 8 months old, EV71 second dose was injected at 9 months old GroupⅣ: JE-Land EV71 were injected at 8 months old, EV71 second dose was injected at 9 months old
干预措施: EV71 (inoculation vaccine) (Biological)
Separate inoculation control group
GroupⅠ: HepB:3 third dose was injected at 6 months old GroupⅡ: MPSV-A:1 was injected at 6 months old, then MPSV-A:1 second dose was injected at 9 months old GroupⅢ: MR was injected at 8 months old GroupⅣ: JE-L was injected at 8 months old
干预措施: EV71 (inoculation vaccine) (Biological)
EV71 inoculation control group
GroupⅠ: EV71 was injected at 8 months old, then EV71 second dose was injected at 9 months old GroupⅡ: EV71 was injected at 8 months old, then EV71 second dose was injected at 9 months old GroupⅢ: EV71 was injected at 8 months old, then EV71 second dose was injected at 9 months old GroupⅣ: EV71 was injected at 8 months old, then EV71 second dose was injected at 9 months old
干预措施: EV71 (inoculation vaccine) (Biological)
结局指标
主要结局
Antibody titer / concentration to vaccination
时间窗: within 90 days after the last vaccination
Blood samples from the participants were collected before and after vaccination, the changes of serum concentration and titer were determined by serum test.
Antibody positive rate to vaccinations
时间窗: within 90 days after the last vaccination
The definition of EV71 vaccine positive for antibody titers \<1:8 before inoculation, antibody titers ≥ 1:8 after inoculation; or before inoculation antibody titer is above 1:8,the titer after vaccination appeared more than 4 times 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 ELISA detection test, measles \>200U/ml positive for rubella \>20U/ml positive or positive before inoculation, antibody positive growth is more than 4 times.Japanese encephalitis vaccine 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. A meningococcal bactericidal antibody level in serum by micro bactericidal antibody test, the antibody titer after inoculation than before inoculation is more than 4 times growth is positive.
次要结局
- Number of Participants at the Injection Site, Solicited Systemic Reactions, or Any Unsolicited Adverse Events(within 90 days after the last vaccination)