Immunity and Safety of Inactivated Enterovirus 71 Vaccine Post-marketing Among Children Aged 6-35 Months in China

Study Overview
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Brief Summary
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This study evaluates three batches consistency, immunity duration and safety of inactivated Enterovirus 71(EV-A71) vaccine(vero cell) post-marketing among children aged 6-35months in China.3000 subjects will be recruited in this study, of who 1500 subjects will be randomly assigned in a ratio of 1:1:1 to receive one of the three batches of EV-A71 vaccines manufactured by 40L capacity reactor, other 1500 subjects will be randomly assigned in a ratio of 1:1:1 to receive one of the three batches of EV-A71 vaccines manufactured by 150L capacity reactor. Vaccine wil be administrated according to a two doses of schedule given at day 0 and 28. Sample will be collected at day 0, day 56 and at month 13 after vaccinaiton.

Official Title
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Three Batches Consistency, Immunity Duration and Safety of Inactivated Enterovirus 71 Vaccine Post-marketing Among Children Aged 6-35 Months in China

Conditions
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Hand, Foot and Mouth Disease

Intervention / Treatment
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* Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
* Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
* Biological: The third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor
* Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor
* Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor
* Biological: The third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy children aged 6-35 months Subjects who have been clinically judged to be healthy by the researcher after being asked about the medical history and related physical examination The subjects' guardians agree the requirements of the protocol and the relevant follow up visits The subjects' guardians agree and sign the informed consent Subjects who have no relocation or long-term travel plan within one year and are able to comply with the requirements of the clinical trial protocol. Exclusion Criteria: Subject who has a medical history of HFMD caused by EV71 or has been vaccinated with EV71 vaccine Subject that has a history of allergies to vaccines or vaccine ingredients, and has serious side effects on vaccines, such as allergies, urticaria, dyspnea, vascular neuroedema or abdominal pain Subject who has congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc. Subject who has a history of epilepsy, convulsion or convulsion, or a family history of mental illness Subject who has autoimmune disease or immune deficiency, or whose parents and siblings have autoimmune disease or immune deficiency Subject who has a history of asthma, vascular and neuroedema, diabetes or malignant tumor Subject who has a thyroid resection history, or received treatment due to thyroid disease in the past 12 months Subject who has an abnormal coagulation function (such as coagulation factor deficiency, coagulant disease, platelet abnormality) or obvious bruising or clotting disorder which was diagnosed by doctors. Asplenia, functional asplenia, or splenectomy due to any circumstances Acute onset of various acute or chronic diseases in the last 7 days Immunosuppressant therapy, antiallergic therapy, cytotoxicity therapy, inhaled corticosteroids (excluding corticosteroid spray therapy for allergic rhinitis, surface corticosteroid therapy for acute non-dermatitis) in the past 6 months Any prior administration of blood products in last 3 months Any prior administration of other research medicines or vaccines in last 1 month Any prior administration of attenuated live vaccine in last 15 days Any prior administration of subunit or inactivated vaccines in last 7 days Under the anti-TB prevention or therapy Underarm temperature > 37.0 ℃ for fever before vaccination Other factors that are not suitable for clinical trials according to the judgment of researchers Exclusion Criteria for the second dose: Have severe allergic reaction after first dose Have severe adverse reactions related to first dose Any situation meet the exclusion criteria stated in the exclusion criteria for first dose Acute infection or illness Other factors that are not suitable for clinical trials according to the judgment of researchers

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 35 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: the first batch vaccine producted by 40 L reactor<br>500 subjects will be randomly received the first batch vaccine producted by 40 L reactor | Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>* 500 subjects will be randomized to receive the first batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>|
| Experimental: the second batch vaccine producted by 40 L reactor<br>500 subjects will be randomly received the second batch vaccine producted by 40 L reactor | Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>* 500 subjects will be randomized to receive the second batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>|
| Experimental: the third batch vaccine producted by 40 L reactor<br>500 subjects will be randomly received the third batch vaccine producted by 40 L reactor | Biological: The third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>* 500 subjects will be randomized to receive the third batch of inactivated EV-A71 vaccine (vero cell) producted by 40 L reactor<br>|
| Experimental: the first batch vaccine producted by 150 L reactor<br>500 subjects will be randomly received the first batch vaccine producted by 150 L reactor | Biological: The first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor<br>* 500 subjects will be randomized to receive the first batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor<br>|
| Experimental: the second batch vaccine producted by 150 L reactor<br>500 subjects will be randomly received the second batch vaccine producted by 150 L reactor | Biological: The second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor<br>* 500 subjects will be randomized to receive the second batch of inactivated EV-A71 vaccine (vero cell) producted by 150 L reactor<br>|
| Experimental: the third batch vaccine proudected by 150 L reactor<br>500 subjects will be randomly received the third batch vaccine producted by 150 L reactor | Biological: The third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor<br>* 500 subjects will be randomized to receive the third batch of inactivated EV-A71 vaccine (vero cell) proudected by 150 L reactor<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Consistency of different batches for geometric mean titre(GMT) after vaccination | Consistency of different batches for GMT of EV-A71 neutralizing antibody on 56 day after vaccination | 56 days after vaccination | 
| Incidence and severity of adverse reactions/adverse events after each dose | Incidence and severity of adverse reactions/adverse events within 1 month after each dose | 1 month after each dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of sever adverse events after vaccination | Incidence of sever adverse events within 13 months after vaccination | 13 months after vaccination | 
| GMTof EV-A71 neutralizing antibody on day 56 after vaccination | GMTof EV-A71 neutralizing antibody on day 56 after vaccination for different batchs | 56 days after vaccination | 
| Positive rate of EV-A71 neutralizing antibody on day 56 after vaccination | Positive rate of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs | 56 days after vaccination | 
| Seroconversion rate of EV-A71 neutralizing antibody on day 56 after vaccination | Seroconversion rate of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs | 56 days after vaccination | 
| Geometric Mean Fold Increase(GMFI) of EV-A71 neutralizing antibody on day 56 after vaccination | Geometric Mean Fold Increase(GMFI) of EV-A71 neutralizing antibody on day 56 after vaccination for different batchs | 56 days after vaccination | 
| GMTof EV-A71 neutralizing antibody on month 13 after vaccination | GMTof EV-A71 neutralizing antibody on month 13 after vaccination for different batchs | 13 months after vaccination | 
| Positive rate of EV-A71 neutralizing antibody on month 13 after vaccination | Positive rate of EV-A71 neutralizing antibody on month 13 after vaccination for different batchs | 13 months after vaccination |