Immunogenicity And Safety of COVID-19 Vaccine , Inactivated Co -Administration With EV71 Vaccine (Vero Cell)

Study Overview
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Brief Summary
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This study is a randomized and controlled phase Ⅳ clinical trial of the COVID-19 vaccine (Vero cell), Inactivated manufactured by Sinovac Research & Development Co., Ltd. The purpose of this study is to evaluate the immunogenicity and safety of COVID-19 vaccine (Vero cell), Inactivated co-administration with EV71 vaccine

Detailed Description
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This study is a randomized and controlled phase Ⅳ clinical trial in children aged 3-5 years old. The purpose of this study is to evaluate the immunogenicity and safety of COVID-19 vaccine (Vero cell), Inactivated co-administration with EV71 vaccine.The COVID-19 vaccine was manufactured by Sinovac Research & Development Co., Ltd, and the EV71 vaccine was manufactured by Sinovac Biotech Co.A total of 520 subjects aged 3-5 years old will be enrolled.Subjects will be randomly divided into 2 groups in a ratio of 1:1.The experimental group is the combined immunization group, which will receive the first dose of COVID-19 vaccine and the second dose of COVID-19 vaccine and EV71 vaccine on day 28;Control group is the Non-combined immunization group , which will receive the first dose of COVID-19 vaccine on day 0 ，the first dose of EV71 vaccine on day 14 ，the second dose of COVID-19 vaccine on day 28 and the second dose of EV71 vaccine on day 42.

Official Title
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A Randomized and Controlled Ⅳ Clinical Trial to Evaluate the Immunogenicity and Safety of COVID-19 Vaccine (Vero Cell), Inactivated Co-administrated With EV71 Vaccine (Vero Cell) in Children Aged 3-5 Years Old

Conditions
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COVID-19

Intervention / Treatment
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* Biological: Experimental Group
* Biological: Control Group


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged 3-5 years ; The subject and/or guardian can understand and voluntarily sign the informed consent form Proven legal identity; Exclusion Criteria: History of contact with a SARS-CoV-2 infection (positive in nucleic acid test) within 14 days; History of multiple system inflammatory syndrome (MIS-C); History of hand, foot and mouth disease, herpetic angina or EV71 vaccination; History of asthma, history of allergy to the vaccine or vaccine components,or serious adverse reactions to the vaccine, such as urticaria, dyspnea,and angioedema; Congenital malformations or developmental disorders, genetic defects,severe malnutrition, etc.; Autoimmune disease (Systemic lupus erythematosus)or immunodeficiency / immunosuppression(HIV,history after organ transplantation)； Severe chronic diseases, severe cardiovascular diseases, hypertension and diabetes that cannot be controlled by drugs, liver or kidney diseases,malignant tumors, etc.; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Thyroid disease or history of thyroidectomy, asplenia,functional asplenia, asplenia or splenectomy resulting from any condition; Diagnosed abnormal blood coagulation function (eg, lack of blood coagulation factors, blood coagulopathy,abnormal platelets) or obvious bruising or blood coagulation; Immunosuppressive therapy, cytotoxic therapy, inhaled corticosteroids (excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) in the past 6 months; History of drug abuse; Receipt of blood products within in the past 3 months; Receipt of other investigational drugs in the past 30 days; Receipt of attenuated live vaccines in the past 14 days; Receipt of inactivated or subunit vaccines in the past 7 days; Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Axillary temperature >37.0°C; The subjects participated in other clinical trials during the follow-up period, or will be planned within 3 months; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 5 Years

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>The experimental group is also called the combined immunization group .260 participants will receive the first dose of COVID-19 vaccine and EV71 vaccine on day 0 and the second dose of COVID-19 vaccine and EV71 vaccine on day 28. | Biological: Experimental Group<br>* The COVID-19 vaccine was manufactured by Sinovac Research & Development Co., Ltd, and the EV71 vaccine was manufactured by Sinovac Biotech Co. The COVID-19 vaccine:600SU inactivated virus in 0.5 mL of aluminium hydroxide solution per injection;The EV71 vaccine:Inactivated EV71 virus antigen no less than 3.0EU in 0.5 mL of aluminium hydroxide solution per injection.<br>* Other names: Combined immunization group;|
| Active Comparator: Control Group<br>The control group is also called the Non-combined immunization group.260 participants will receive the first dose of COVID-19 vaccine on day 0,the first dose of EV71 vaccine on day 14,the second dose of COVID-19 vaccine on day 28 and the second dose of EV71 vaccine on day 42. | Biological: Control Group<br>* The COVID-19 vaccine was manufactured by Sinovac Research & Development Co., Ltd, and the EV71 vaccine was manufactured by Sinovac Biotech Co. The COVID-19 vaccine:600SU inactivated virus in 0.5 mL of aluminium hydroxide solution per injection;The EV71 vaccine:Inactivated EV71 virus antigen no less than 3.0EU in 0.5 mL of aluminium hydroxide solution per injection.<br>* Other names: Non-combined immunization group;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-Seroconversion rate of the neutralizing antibody to live SARS-CoV-2 | Seroconversion rate of the neutralizing antibody to live SARS-CoV-2 at day 28 after the second dose of COVID-19 vaccine | Day 28 after the second dose of COVID-19 vaccine | 
| Immunogenicity index-Seroconversion rate of the neutralizing antibody to EV71 | Seroconversion rate of the neutralizing antibody to EV71 at day 28 after the second dose of EV71 vaccine | Day 28 after the second dose of EV71 vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index-Seropositivity rate of the neutralizing antibody to live SARS-CoV-2 | Seropositivity rate of the neutralizing antibody to live SARS-CoV-2 at day 28 after the second dose of COVID-19 vaccine. | Day 28 after the second dose of COVID-19 vaccine | 
| Immunogenicity index- GMT of the neutralizing antibody to live SARS-CoV-2 | GMT of the neutralizing antibody to live SARS-CoV-2 at day 28 after after the second dose of COVID-19 vaccine. | Day 28 after the second dose of COVID-19 vaccine | 
| Immunogenicity index-GMI of the neutralizing antibody to live SARS-CoV-2 | GMI of the neutralizing antibody to live SARS-CoV-2 at day 28 after after the second dose of COVID-19 vaccine. | Day 28 after the second dose of COVID-19 vaccine | 
| Immunogenicity index-Seropositive rate of the neutralizing antibody to EV71 | Seropositive rate of the neutralizing antibody to EV71 at day 28 after the second dose of EV71 | Day 28 after the second dose of EV71 | 
| Immunogenicity index-GMT of the neutralizing antibody to EV71 | GMT of the neutralizing antibody to EV71 at day 28 after the second dose of EV71 | Day 28 after the second dose of EV71 | 
| Immunogenicity index-GMI of the neutralizing antibody to EV71 | GMI of the neutralizing antibody to EV71 at day 28 after the second dose of EV71 | Day 28 after the second dose of EV71 | 
| Safety index-Incidence of the adverse reactions | Incidence of the adverse reactions from day 0 to day 7 after each dose | From day 0 to day 7 after each dose | 
| Safety index-Incidence of the adverse reactions | Incidence of the adverse reactions from day 0 to 28 days after the last dose | From day 0 to 28 days after the last dose | 
| Safety index-Incidence of the serious adverse events and the adverse events of special interest | Incidence of the serious adverse events and the adverse events of special interest from the beginning vaccination to 6 months after the last dose | From the beginning vaccination to 6 months after the last dose |