A Phase III 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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A phase III clinical trial of the study of quadrivalent influenza vaccine developed by Sinovac Biotech will be conducted in Chinese children aged 6 to 35 months. The trial is an randomized, double-blind and active controlled study. The objective of this study is to evaluate the Immunogenicity and safety of the vaccine.

Detailed Description
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A phase III clinical trial of the study of quadrivalent influenza vaccine developed by Sinovac Biotech will be conducted in Chinese children aged 6 to 35 months. The trial is an randomized, double-blind and active controlled study. The objective 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 3300 subjects will be enrolled. The subjects 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, according to the immunization schedule of day 0,28 in each group.

Official Title
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An 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 allergy to the vaccine or vaccine components, or serious adverse reactions to the vaccine, such as urticaria, dyspnea, angioedema and asthma; 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 (such as systemic lupus erythematosus) or immunodeficiency / immunosuppression (such as HIV, after organ transplantation) 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; Continuous use of corticosteroids or other immunosuppressive agents for ≥ 14 days within the past 6 months (excluding allergic rhinitis corticosteroid spray therapy, acute noncomplicated dermatitis superficial corticosteroid therapy) and cytotoxic 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group of quadrivalent influenza vaccine(0.25ml)<br>1100 subjects phase III will receive two doses of quadrivalent influenza vaccine(0.25ml) according to 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 njection.The routine of administration is Intramuscular injection into deltoid region.And the immunization schedule is two doses 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) according to 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 njection.The routine of administration is Intramuscular injection into deltoid region.And the immunization schedule is two doses 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) according to 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 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) according to 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 vaccine on day 0, 28.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates of HI antibody | Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, B Victoria and B Yamagata. Seroconversion was defined as pre-vaccination titer <1：10 and post-vaccination titer ≥1:40, and Significant increase was defined as pre-vaccination titer≥1:40 and ≥ 4-fold increase of post-vaccination titer. | 28 days after full schedule immunization | 
| Geometric Mean Titers (GMTs) of HI antibody | Anti-influenza antibody levels were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria, B Yamagata. | 28 days after full schedule immunization | 
| Number of Participants With Seroprotection to Influenza Vaccine Antigens | Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, B Victoria and B Yamagata. Seroprotection was defined as an antibody titer ≥1:40 at pre-vaccination and at post-final vaccination. | 28 days after full schedule immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMIs of HI antibody | Anti-influenza antibody were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria, B Yamagata. GMI is the increase fold of GMT post vaccination compared with pre vaccination | 28 days after full schedule immunization | 
| Incidence of adverse reactions | Incidence of adverse reaction 0-30 days after each dose | 0-30 days after each dose | 
| Incidence of adverse reactions | Incidence of adverse reaction 0-7 days after each dose | 0-7 days after each dose | 
| Incidence of Serious adverse events | Incidence of serious adverse events from beginning of vaccination until 6 months after the last dose | Since the beginning of vaccination until 6 months after the last dose | 
| Incidence of AESI | Incidence of AESI since the beginning of vaccination until 6 months after the last dose | since the beginning of vaccination until 6 months after the last dose |