Clinical Trial to Evaluate the Safety and Immunogenicity of Quadrivalent Influenza Vaccine (15µg/0.5ml)

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 subjects aged over 3 years

Detailed Description
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This study is a phase I& III clinical trial. Phase I is open-labelled, and phase III is randomized, double-blind, active-controlled. The purpose of this study is to evaluate the safety and immunogenicity of the quadrivalent influenza vaccine (QIV) (experimental vaccine) manufactured by Sinovac Biotech Co., Ltd in subjects aged over 3 years. In phase I, 60 volunteers received single dose QIV (15µg/0.5ml). In phase III, 2320 volunteers were assigned to receive single dose QIV (15µg/0.5ml) or two commercial trivalent influenza vaccines (TIVs) (15µg/0.5ml) in a ratio of 2:1:1. The commercial TIVs were also 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 Over 3 Years.

Conditions
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Seasonal Influenza

Intervention / Treatment
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* 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 volunteers aged ≥3 years; Proven legal identity; Participants or (and) guardians of the participants should be capable of understanding the written consent form, and such form should be signed prior to enrolment; Exclusion Criteria: Prior vaccination with influenza vaccine of the current year; History of influenza within 6 months prior to study entry; Axillary temperature > 37.0 °C; History of allergy to any vaccine, or any ingredient of the experimental vaccine, especially eggs, egg albumin, etc.; Serious adverse reaction(s) to vaccination, such as urticaria, dyspnea, angioneurotic edema, abdominal pain, etc.; Severe/uncontrollable nervous system disease (epilepsy, seizures or convulsions) or mental illness; Autoimmune disease or immunodeficiency/immunosuppressive, or any immunosuppressant receipt within 6 months prior to the study entry; History of asthma, thyroidectomy, angioedema, diabetes or malignancy; No spleen, or functional no spleen, or splenectomy.

Ages Eligible for Study
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Minimum Age: 3 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
Interventional Model Description: The phase I clinical trial has single arm, and the phase III clinical trial has 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>* Received single dose QIV (15µg/0.5ml)<br>|
| Experimental: Experimental group-phase III<br>Quadrivalent influenza vaccine | Biological: Quadrivalent influenza vaccine<br>* Received single dose QIV (15µg/0.5ml)<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>* Received single dose TIV which contains B/Victoria strain (15µg/0.5ml)<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>* Received single dose TIV which contains B/Yamagata strain (15µg/0.5ml)<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 the ratio of geometric mean titer of hemagglutination inhibition (HI) antibody titer (experimental group/control group)≥2/3. | Immunogenicity index, One of the standard to evaluate the experimental vaccine is non-inferior to the control vaccines | 28 days after the injection | 
| 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 non-inferior to the control vaccines | 28 days after the injection | 

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 the injection | 
| 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 the injection | 
| The 95% CI lower limit of seroconversion rate of HI antibodies in the subjects aged 3-59 years≥40% | Immunogenicity index | 28 days after the injection | 
| The 95% CI lower limit of seroconversion rate of HI antibodies in the subjects aged over 60 years≥30% | Immunogenicity index | 28 days after the injection | 
| The seroprotective rate (HI antibody titer≥1:40) in the subjects aged 3-59 years ≥70% | Immunogenicity index | 28 days after the injection | 
| The seroprotective rate (HI antibody titer≥1:40) in the subjects aged over 60 years ≥60% | Immunogenicity index | 28 days after the injection | 
| The geometric mean increase (GMI) in the subjects aged 3-59 years >2.5 | Immunogenicity index | 28 days after the injection | 
| The geometric mean increase (GMI) in the subjects aged over 60 years >2.0 | Immunogenicity index | 28 days after the injection | 
| 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 the injection | 
| 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 the injection | 
| The incidence of the solicited local and general adverse reactions on day 0-7 | Safety index, The adverse reactions refers to the adverse events which considered related to the vaccination | 0-7 days after the injection | 
| The incidence of the unsolicited adverse events on day 0-28 | Safety Index | 0-28 days after the injection | 
| The incidence of the serious adverse events within 6 months after the injection | Safety Index | Within 6 months after the injection | 

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