Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine (7.5μg/0.25ml)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of quadrivalent influenza vaccine in healthy children aged 6-35 months.

Detailed Description
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The study includes open-labelled phase I and randomized, double-blind, controlled phase III clinical trial. In the phase I, 20 healthy Chinese children aged 6-35 months were administered with two doses of QIV (7.5μg/0.25ml). In the phase Ⅲ clinical trial, 2320 children were assigned to QIV group, TIV (B/Victoria) group and TIV (B/Yamagata) group in a 2:1:1 ratio. All vaccines were manufactured by Sinovac Biotech Co., Ltd.

Official Title
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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 6-35 Months

Conditions
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Seasonal Influenza

Intervention / Treatment
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* Biological: Quadrivalent influenza vaccine
* Biological: Quadrivalent influenza vaccine
* Biological: Trivalent influenza vaccine (contains B/Victoria strain)
* Biological: Trivalent influenza vaccine (contains B/Yamagata strain)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteer between 6 - 35 months old; Term birth; Birth weight >2500g; Proven legal identity; Written consent of the guardian(s) of the volunteer; Exclusion Criteria: Received seasonal influenza vaccine in the current year; Suffering from seasonal influenza in the past 6 moths; Axillaty temperature > 37.0 °C; History of allergy to any vaccine or vaccine ingredient; History of serious adverse reaction(s) to vaccination, such as urticaria, difficulty in breathing, angioneurotic edema, abdominal pain, etc; Autoimmune disease or immunodeficiency; Congenital malformation, developmental disorders; Severe malnutrition; Diagnosed coagulation function abnormal (e.g., coagulation factor deficiency, coagulation disorder, or platelet abnormalities) , or obvious bruising or coagulation disorders; History of epilepsy (except febrile seizures occurred < 2 years of age or pure epilepsy occurred within the past 3 years that does not need treatment) Chronic diseases (e.g., viral hepatitis, tuberculosis, diabetes, blood diseases, or neurological disorders) Acute disease or acute stage of chronic disease; Receipt of any of the following products: Any subunit vaccine or inactivated vaccine (e.g., pneumococcal vaccine) or treatment of allergy within 14 days prior to study entry; Any live attenuated vaccine within 30 days prior to study entry; Any other investigational medicine(s) or vaccine within 30 days prior to study entry; Blood product within 3 months prior to study entry; Any immunosuppressant, cytotoxic medicine, or inhaled corticosteroids (except corticosteroid spray for treatment of allergic rhinitis or corticosteroid treatment on surface for acute non-complicated dermatitis) within 6 month prior to study entry; Participate or will participate in other clinical trial(s) during this study; Based on the judgment of investigator(s) or the Ethic Committee, there was any condition indicating that the subject should be excluded;

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
Interventional Model Description: The phase Ⅰ clinical trial was a single arm.The phase Ⅲ was 3 parallel arms.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group-phase Ⅰ<br>Quadrivalent influenza vaccine | Biological: Quadrivalent influenza vaccine<br>* One dose of quadrivalent influenza vaccine: 0.25 ml per dose containing 7.5μg antigen.<br>|
| Experimental: Experimental group-phase Ⅲ<br>Quadrivalent influenza vaccine | Biological: Quadrivalent influenza vaccine<br>* One dose of quadrivalent influenza vaccine: 0.25 ml per dose containing 7.5μg antigen.<br>|
| Active Comparator: Control group 1-phase Ⅲ<br>Trivalent influenza vaccine (contains B/Victoria strain) | Biological: Trivalent influenza vaccine (contains B/Victoria strain)<br>* One dose of trivalent influenza vaccine (contains B/Victoria strain): 0.25 ml per dose containing 7.5μg antigen.<br>|
| Active Comparator: Control group 2-phase Ⅲ<br>Trivalent influenza vaccine (contains B/Yamagata strain) | Biological: Trivalent influenza vaccine (contains B/Yamagata strain)<br>* One dose of trivalent influenza vaccine (contains B/Yamagata strain): 0.25 ml per dose containing 7.5μg antigen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The lower limit of 95% confidence intervals (95%CI) of geometric mean titer (GMT) ratio (experimental group/control group) of hemagglutination inhibition (HI) antibody titer≥2/3. | Immunogenicity index, One of the standard to evaluate the experimental vaccine is non-inferior to the control vaccines. | 28 days after two doses immunization | 
| The lower limit of 95% CI of the seroconversion rate difference (experimental group-control group)≥-10%. | Immunogenicity index, Another standard to evaluate the experimental vaccine is non-inferior to the control vaccines. | 28 days after two doses immunization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The lower limit of 95%CI of the ratio of GMT (experimental group/control group) >1.5. | Immunogenicity index, One of the standard to evaluate the experimental vaccine is superior to the control vaccines for specific antigen type. | 28 days after two doses immunization | 
| The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)>10% | Immunogenicity index, Another standard to evaluate the experimental vaccine is superior to the control vaccines for specific antigen type. | 28 days after two doses immunization | 
| The lower limit of 95% CI of seroconversion rate for each HI antibody after two doses immunization≥40%. | Immunogenicity index | 28 days after two doses immunization | 
| The seroprotective rate (HI antibody titer≥1:40) of each HI antibody after two doses immunization≥70%. | Immunogenicity index | 28 days after two doses immunization | 
| The geometric mean increase (GMI) of each HI antibody after two doses immunization >2.5. | Immunogenicity index | 28 days after two doses immunization | 
| The lower limit of 95%CI of the ratio of GMT(experimental group/control group)≥2/3, in the subjects whose pre-immune HI antibody titer<1:40 | Immunogenicity index | 28 days after two doses immunization | 
| The lower limit of 95% CI of the difference of HI antibody seroconversion rate (experimental group-control group)≥-10%, in the subjects whose pre-immune HI antibody titer<1:40. | Immunogenicity index | 28 days after two doses immunization | 
| The incidence of the solicited local and general adverse reactions 0-7 days after each immunization. | Safety index, The adverse reactions refers to the adverse events which were considered related to the vaccination. | 0-7 days | 
| The incidence of the unsolicited adverse events 0-28 days after each immunization | Safety Index | 0-28 days after each dose immunization | 
| The incidence of the serious adverse events within 7 months after the first immunization. | Safety Index | Within 7 months after the first dose immunization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza Vaccine, Quadrivalent, Trivalent, Children