Evaluation of the Safety and Immunogenicity of Simultaneously Administration of EV71 Vaccine and Influenza Vaccine

Study Overview
=================
Brief Summary
-----------------
Subjects will be recruited and divided into 3 groups: Experimental Group (378 subjects): combined immunization of EV71 vaccine and influenza vaccine; Control Group A (378 subjects): EV71 vaccine only; Control Group B (378 subjects): influenza vaccine only; All blood samples will be collected before and one month after vaccinatioin. The immunogenicity and safety of both experimental and control groups will be compared and the data be analyzed.

Detailed Description
-----------------
To further evaluate the feasibility of simultaneously administration of EV71 vaccine and flu vaccine, we design this clinical trial to test its immunogenicity and safety. 1134 subjects aged from 6 to 11 months old are divided into one experimental group and two control groups (control group A and B). 378 subjects from the experimental group will be simultaneously administrated with one dose of EV71 vaccine (0.5 ml) and one dose of influenza vaccine (0.25 ml). One month later, they are going to receive a second dose of EV71 vaccine and influenza vaccine, simultaneously. Blood samples are collected before the first vaccination, and one month following the second vaccination. 378 subjects from the control group A will be only administrated with two doses of EV71 vaccine (0.5 ml) (1 month apart). Blood samples are collected before the first vaccination, and one month following the second vaccination. 378 subjects from the control group B will be only administrated with two doses of influenza vaccine (0.25 ml) (1 month apart). Blood samples are collected before the first vaccination, and one month following the second vaccination. To evaluate the immunogenicity, we will detect and compare the neutralization antibody levels, the seroprotection rates, and antibody geometric mean concentrations. The safety of all groups will be monitored as well.

Official Title
-----------------
A Randomized, Controlled, Multicenter Phase 4 Clinic Trial to Evaluate the Safety and Immunogenicity of Simultaneously Administration of EV71 Vaccine and Influenza Vaccine (Split Virion),Inactivated

Conditions
-----------------
Enterovirus Infections, Influenza

Intervention / Treatment
-----------------
* Biological: EV71 vaccine and influenza vaccine
* Biological: EV71 vaccine
* Biological: influenza vaccine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: subjects aged from 6-11 months old at the date of recruitment; with informed consent signed by parent(s) or guardians; parent(s) or guardians are able to attend all planned clinical appointments and comply with all study instructions; subjects not receive any vaccination within 14 days at the date of recruitment; subjects have not been vaccinated with EV71 vaccine, seasonal flu vaccine; subjects with no medical history of EV71 infection; axillary temperature ≤37.0℃ Exclusion Criteria: subject who has a medical history with Hypersensitiveness, eclampsia, epilepsy, cerebropathia and neurological illness; allergic to any ingredient of vaccine or with allergy history to any vaccine; subjects with immunodeficency or suspected impairment of immunologic function (e.g. caused by HIV), or subjects are in the process of immunosuppressor therapy(Taking orally injecting of steroid hormone); administration of immunoglobulins within 30 days prior to this study; acute febrile disease(temperature ≥ 37.0°C) or infectious disease; have a clearly diagnosed history of thrombocytopenia or other coagulopathy, may cause contraindications for subcutaneous injection; any serious chronic illness, acute infectious diseases, or respiratory diseases; severe cardiovascular disease, liver and kidney diseases or diabetes mellitus with complications; any kind of infectious, purulent, or allergic skin diseases; any other factor that makes the investigator determines the subject is unsuitable for this study.

Ages Eligible for Study
-----------------
Minimum Age: 6 Months
Maximum Age: 11 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: experimental group<br>378 subjects from the experimental group will be simultaneously administrated with one dose of EV71 vaccine (0.5 ml) and one dose of influenza vaccine (0.25 ml). One month later, they are going to receive a second dose of EV71 vaccine and influenza vaccine, simultaneously. | Biological: EV71 vaccine and influenza vaccine<br>* simultaneously administrated with EV71 vaccine and influenza vaccine<br>|
| Active Comparator: control group A<br>378 subjects from the control group A will be only administrated with two doses of EV71 vaccine (0.5 ml) (1 month apart). | Biological: EV71 vaccine<br>* administrated with EV71 vaccine only<br>|
| Active Comparator: control group B<br>378 subjects from the control group B will be only administrated with two doses of influenza vaccine (0.25 ml) (1 month apart). | Biological: influenza vaccine<br>* administrated with influenza vaccine only<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate I | the rate of positive seroconversion against EV71 | Baseline (before vaccination) and 1 month after the last dose | 
| Seroconversion rate II | the rate of positive seroconversion against Influenza A (H3N2, H1N1) and B Type viruses | Baseline (before vaccination ) and 1 month after the last dose | 
| Geometric mean titer (GMT) I | Measure neutralizing antibody titers against EV71 | Baseline (before vaccination) and 1 month after the last dose | 
| Geometric mean titer (GMT) II | Measure neutralizing antibody titers against Influenza A (H3N2, H1N1) and B Type viruses | Baseline (before vaccination) and 1 month after the last dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| adverse events following vaccination | analyse the numbers and rates of participants who experience adverse events following immunization | 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
EV71 vaccine, influenza vaccine, simultaneously administration