A Clinical Trial of Quadrivalent Influenza Vaccine in Healthy Subjects Aged 6 to 35 Months

Study Overview
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Brief Summary
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The study of quadrivalent influenza vaccine manufactured by Sinovac Biotech Co., Ltd will conduct in two phases,the phaseⅠclinical trial of the study will be open-label design,and the phase III clinical trial of the study will be randomized, double-blind, active controlled design.the purpose of this study is to evaluate the safety and immunogenicity of quadrivalent influenza vaccine in healthy subjects aged 6 to 35 months.

Detailed Description
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This study of quadrivalent influenza vaccine will be open-label design in phase Ⅰ and randomized, double-blind, active controlled design in phase III.The quadrivalent influenza vaccine was manufactured by Sinovac Biotech Co., Ltd. The purpose of this study is to evaluate the safety and immunogenicity of quadrivalent influenza vaccine(0.25ml and 0.5ml) manufactured by Sinovac Biotech Co., Ltd in healthy infants aged from 6 to 35 months. A total of 3330 subjects including 30 subjects in phase Ⅰ and 3300 subjects in phase III will be enrolled. The subjects in phase Ⅰ will receive 2 doses of quadrivalent influenza vaccine(0.5ml) on the immunization schedule of day 0,28.The subjects in phase III will be randomly assigned to 4 groups in a 2:2:1:1 ratio and subjects will receive two doses of quadrivalent influenza vaccine(0.25ml or 0.5ml) or trivalent influenza vaccine(BV or BY), respectively,on the immunization schedule of day 0,28 in each group.

Official Title
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An Open Phase I and Randomized, Double-blind, Controlled Phase III Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine in Healthy Subjects Aged 6 to 35months.

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: Quadrivalent influenza vaccine(0.25ml)
* Biological: Quadrivalent influenza vaccine(0.5ml)
* Biological: Trivalent influenza vaccine(BV)
* Biological: Trivalent influenza vaccine(BY)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants aged 6-35 months; Proven vaccination certificate and birth certificate; The subjects' guardians can understand and voluntarily sign the informed consent form. 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; Axillary temperature >37.0°C; 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.; Severe chronic diseases(Such as down syndrome, diabetes, sickle cell anaemia or neurological disorders); Severe neurological disease (epilepsy, convulsions or convulsions) or mental illness; Autoimmune disease or immunodeficiency / immunosuppression; 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; Acute diseases or acute exacerbation of chronic diseases in the past 3 days; 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; Participated in other clinical trials before enrollment and in the follow-up period, or plans to participate in other clinical trials during the clinical trial; 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: 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Safety group<br>PhaseⅠ,30 subjects will receive two doses of quadrivalent influenza vaccine(0.5ml) on the immunization schedule of day 0,28. | Biological: Quadrivalent influenza vaccine(0.25ml)<br>* 7.5 ug hemagglutinin (HA) of each of the four influenza strains in 0.25 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administration 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 of quadrivalent influenza vaccine(0.25ml)<br>1100 subjects phase III will receive two doses of quadrivalent influenza vaccine(0.25ml) on the immunization schedule of day 0,28. | Biological: Quadrivalent influenza vaccine(0.25ml)<br>* 7.5 ug hemagglutinin (HA) of each of the four influenza strains in 0.25 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administration 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 of quadrivalent influenza vaccine(0.5ml)<br>1100 subjects phase III will receive two doses of quadrivalent influenza vaccine(0.5ml) on the immunization schedule of day 0,28. | Biological: Quadrivalent influenza vaccine(0.5ml)<br>* 15 ug 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 administration is Intramuscular injection into deltoid region.And the immunization schedule is two doses of quadrivalent influenza vaccine on day 0, 28.<br>|
| Active Comparator: Control Group of trivalent influenza vaccine(BV)<br>550 subjects phase III will receive two doses of trivalent influenza vaccine(BV) on the immunization schedule of day 0,28. | Biological: Trivalent influenza vaccine(BV)<br>* 7.5μg inactivated influenza antigen (H1N1, H3N2, Victoria) of each of the trivalent influenza vaccine in 0.25 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administration is Intramuscular injection into deltoid region.And the immunization schedule is two doses of quadrivalent influenza vaccine on day 0, 28.<br>|
| Active Comparator: Control Group of trivalent influenza vaccine(BY)<br>550 subjects phase III will receive two doses of trivalent influenza vaccine(BY) on the immunization schedule of day 0,28. | Biological: Trivalent influenza vaccine(BY)<br>* 7.5μg inactivated influenza antigen (H1N1, H3N2, and Yamagata) of each of the trivalent influenza vaccine in 0.25 mL of sodium chloride, disodium hydrogen phosphate, sodium dihydrogen phosphate per injection.The routine of administration is Intramuscular injection into deltoid region.And the immunization schedule is two doses of quadrivalent influenza vaccine on day 0, 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunogenicity index of seroconversion rate | HI antibody seroconversion rate 28 days after full schedule immunization | 28 days after full schedule immunization | 
| Immunogenicity index of seroprotection rate | HI antibody seroprotection rate 28 days after full schedule immunization | 28 days after full schedule immunization | 
| Immunogenicity index of GMT | HI antibody GMT increase folds 28 days after full schedule immunization | 28 days after full schedule immunization | 
| Safety index of the incidence of adverse reaction | Incidence of adverse reaction 0-28 days after each dose | 0-28 days after each dose | 
| Safety index of the incidence of adverse reaction | Incidence of adverse reaction 0-7 days after each dose | 0-7 days after each dose | 
| Safety index of the incidence of abnormal blood biochemical indexes | The incidence of abnormal blood biochemical indexes 3 days after each dose | 3 days after each dose | 
| Safety index of the incidence of SAE | Incidence of SAE since the beginning of vaccination until 6 months after full course vaccination | Since the beginning of vaccination until 6 months after full course vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety index of the incidence of AESI | Incidence of AESI since the beginning of vaccination until 6 months after full course vaccination | Since the beginning of vaccination until 6 months after full course vaccination |