A Clinical Trial of Quadrivalent Influenza Vaccine in Children Aged 3-8 Years Old

Study Overview
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Brief Summary
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This is an open-label, randomized and controlled phase Ⅳ clinical trial of quadrivalent influenza vaccine manufactured by Sinovac Biotech Co. , the purpose of this study is to compare the immunogenicity and safety after 1 dose of quadrivalent influenza vaccine with that of 2 doses in vaccine-unprimed children aged 3-8 years old,to compare the immunogenicity and safety after 1 dose of quadrivalent influenza vaccine in vaccine-unprimed children aged 3-8 years old with that of 1 dose in vaccine-primed children and to compare the immunogenicity and safety after 2 doses of quadrivalent influenza vaccine in vaccine-unprimed children aged 3-8 years old with that of 1 dose in vaccine-primed children.

Detailed Description
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This study is open-label, randomized and controlled phase Ⅳ clinical trial of quadrivalent influenza vaccine.The purpose of this study is to compare the immunogenicity and safety after 1 dose of quadrivalent influenza vaccine with that of 2 doses in vaccine-unprimed children aged 3-8 years old,to compare the immunogenicity and safety after 1 dose of quadrivalent influenza vaccine in vaccine-unprimed children aged 3-8 years old with that of 1 dose in vaccine-primed children and to compare the immunogenicity and safety after 2 doses of quadrivalent influenza vaccine in vaccine-unprimed children aged 3-8 years old with that of 1 dose in vaccine-primed children.A total of 600 subjects including 400 vaccine-unprimed children and 200 vaccine-primed children will be enrolled,400 vaccine-unprimed children will be randomly divided into two groups in a 1:1 ratio.Subjects in group 1(experimental group 1 ) will receive two doses of quadrivalent influenza vaccine on the immunization schedule of day 0,28 and subjects in group 2 (experimental group 2) will receive one dose of quadrivalent influenza vaccine.200 vaccine-primed children (experimental group 3) will receive one dose of quadrivalent influenza vaccine.

Official Title
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An Exploratory Clinical Trial to Evaluate the Immunogenicity and Safety of One vs Two Doses of Quadrivalent Influenza Vaccine in Children Aged 3-8 Years Old

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: Two doses of quadrivalent influenza vaccine
* Biological: One dose of quadrivalent influenza vaccine


Participation Criteria
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Eligibility Criteria
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vaccine-unprimed children Inclusion Criteria: Healthy children aged 3-8 years; The subjects' guardians can understand and voluntarily sign the informed consent form; Proven legal identity. Exclusion Criteria: Received any circulating seasonal influenza vaccine prior to enrollment or had an influenza vaccine schedule during the study; Suffering from seasonal influenza in the past 6 moths; 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 or immunodeficiency / immunosuppression; 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 inactivated or subunit vaccines in the past 7 days; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; According to the investigator's judgment, the subject has any other factors that are not suitable for participating in the clinical trial. vaccine-primed children Inclusion Criteria: Healthy children aged 3-8 years; The subjects' guardians can understand and voluntarily sign the informed consent form; Proven legal identity; Received at least 1 dose of seasonal influenza vaccine in previous epidemic seasons Exclusion Criteria: Received an seasonal influenza vaccine for the current epidemic season (2020-2021 epidemic season) prior to enrollment, or had an influenza vaccine schedule during the study; Suffering from seasonal influenza in the past 6 moths; 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 or immunodeficiency / immunosuppression; 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; Acute diseases or acute exacerbation of chronic diseases in the past 7 days; Axillary temperature >37.0°C; 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: 8 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 ：Vaccine-unprimed subjects with two doses<br>200 vaccine-unprimed children will receive two doses of quadrivalent influenza vaccine on the immunization schedule of day 0,28. | Biological: Two doses of quadrivalent influenza vaccine<br>* 15ug hemagglutinin (HA) of each of the four influenza strains in 0.5 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administation is Intramuscular injection into deltoid region.And the immunization schedule is two doses of quadrivalent influenza vaccine on day 0, 28.<br>|
| Experimental: Experimental Group ：Vaccine-unprimed subjects with one dose<br>200 vaccine-unprimed children will receive one dose of quadrivalent influenza vaccine. | Biological: One dose of quadrivalent influenza vaccine<br>* 15ug hemagglutinin (HA) of each of the four influenza strains in 0.5 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administation is Intramuscular injection into deltoid region.And the immunization schedule is one dose of quadrivalent influenza vaccine on day 0.<br>|
| Experimental: Experimental Group：Vaccine-primed subjects with one dose<br>200 vaccine-primed children will receive one dose of quadrivalent influenza vaccine. | Biological: One dose of quadrivalent influenza vaccine<br>* 15ug hemagglutinin (HA) of each of the four influenza strains in 0.5 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administation is Intramuscular injection into deltoid region.And the immunization schedule is one dose of quadrivalent influenza vaccine on day 0.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index of the seroconversion rate | The seroconversion rate of each influenza strain after each dose of quadrivalent influenza vaccine | 28 days after the vaccination of the last dose | 
| Immunogenicity index of the seroprotective rate | The seroprotective rate of each influenza strain after each dose of quadrivalent influenza vaccine | 28 days after the vaccination of the last dose | 
| Immunogenicity index of the GMT | The GMT of each influenza strain after each dose of quadrivalent influenza vaccine | 28 days after the vaccination of the last dose | 
| Immunogenicity index of the GMI | The GMI of each influenza strain after each dose of quadrivalent influenza vaccine | 28 days after the vaccination of the last dose | 
| Safety index of the incidence of adverse reactions | The incidence of adverse reactions within 0-7 days after each dose | From day 0 to day 7 after each dose vaccination | 
| Safety index of the incidence of adverse reactions | The incidence of adverse reactions within 0-28 days after each dose | From day 0 to day 28 after each dose vaccination | 
| Safety index of the incidence of serious adverse events(SAEs) | The incidence of serious adverse events from the beginning of vaccination to 28 days after the last dose | From the beginning of the vaccination to 28 days after the whole-schedule vaccination |