Clinical Trial of Quadrivalent Influenza Virus Split Vaccine

Study Overview
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Brief Summary
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To evaluate the immunogenicity and safety of 2 doses of quadrivalent influenza virus split vaccine in healthy population aged 6-35 month., so as to provide a data support for phase III clinical trials.

Official Title
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Immunogenicity and Safety of Quadrivalent Influenza Vaccine In 6 to 35 Months Population: a Randomized, Double-blind, Parallel-group Ⅱ Phase of Clinical Trials

Conditions
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Influenza

Intervention / Treatment
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* Biological: 0.5ml Quadrivalent influenza vaccine
* Biological: 0.25ml Quadrivalent influenza vaccine
* Biological: 0.25ml Trivalent influenza vaccine(B/V)
* Biological: 0.25ml Trivalent influenza vaccine(B/Y)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants aged 6-35 months. Volunteer legal guardian or client informed consent, voluntarily participate in and sign informed consent. The volunteer legal guardian or client has the ability (non-illiterate) to understand the study procedures, to use a thermometer, scale, and fill in a diary card as required, and be able to complete the clinical study in compliance with the clinical trial protocol. Exclusion Criteria: The underarm body temperature on the day of enrollment was > 37.0℃. Have been suffering from influenza within the previous 3 months (confirmed by either clinical, serological or microbiological methods). Any previous influenza vaccination (registered or experimental) within 6 months or any planned influenza vaccination during the study period. Allergic to any component of the vaccine, a history of allergic reactions to eggs or gentamicin sulfate. A history of severe allergy to any vaccine or drug. Preterm birth (delivered before 37 weeks of gestation), low birth weight baby (birth weight < 2300g for girls, <2500g for boys). Dystocia, asphyxia rescue, nervous system damage history; Congenital malformations or developmental disorders, genetic defects, severe malnutrition, etc. Acute illness, severe chronic illness or acute attack of chronic disease on the day of vaccination; A history of live attenuated vaccination within 14 days prior to vaccination and a history of other vaccinations within 7 days prior to vaccination; Patients who received immunoenhancement or inhibitor therapy within 3 months (continued oral or intravenous administration for more than 14 days); Congenital or acquired immune deficiency, HIV infection, lymphoma, leukemia or other autoimmune diseases; History of asthma, past two years of instability requiring emergency treatment, hospitalization, intubation, oral or intravenous administration of corticosteroids; Have received blood or blood-related products; A history of convulsion, epilepsy, encephalopathy, guillain-barre syndrome, a history of mental illness or a family history; A history of abnormal coagulation function (such as coagulation factor deficiency, coagulation disease); Planning to relocate before the end of the study or to leave for an extended -period during the scheduled study visit; Participating in or planning to participate in other clinical trials in the near future; The investigators determined that any conditions were inappropriate to participate 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: Quadrivalent influenza vaccine HD<br>Participants randomized to receive two injections of 0.5 mL quadrivalent influenza vaccine at Day 0 and 28. | Biological: 0.5ml Quadrivalent influenza vaccine<br>* The inactivated split virion vaccines contained 15 μg of each hemagglutinin antigen of influenza A/H1N1, A/H3N2, B/Victoria and B/Yamagata strains<br>|
| Experimental: Quadrivalent influenza vaccine LD<br>Participants randomized to receive two injections of 0.25 mL quadrivalent influenza vaccine at Day 0 and 28. | Biological: 0.25ml Quadrivalent influenza vaccine<br>* The inactivated split virion vaccines contained 7.5 μg of each hemagglutinin antigen of influenza A/H1N1, A/H3N2, B/Victoria and B/Yamagata strains<br>|
| Active Comparator: Trivalent influenza vaccine Victoria<br>Participants randomized to receive two injections of 0.25 mL trivalent influenza vaccine containing B/Victoria strain at Day 0 and 28. | Biological: 0.25ml Trivalent influenza vaccine(B/V)<br>* The inactivated split virion vaccines contained 7.5 μg of each hemagglutinin antigen of influenza A/H1N1, A/H3N2 and B/Victoria strains<br>|
| Active Comparator: Trivalent influenza vaccine Yamagata<br>Participants randomized to receive two injections of 0.25 mL trivalent influenza vaccine containing B/Yamagata strain at Day 0 and 28. | Biological: 0.25ml Trivalent influenza vaccine(B/Y)<br>* The inactivated split virion vaccines contained 7.5 μg of each hemagglutinin antigen of influenza A/H1N1, A/H3N2 and B/Yamagata strains<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| seroconversion rate of HI antibodies | 28 days after receiving two doses of vaccine in subjects aged 6-35 months, seroconversion rate of HI antibodies against any subtype of influenza virus in each group. | 56 days | 
| seroprotection rate of HI antibodies | 28 days after receiving two doses of vaccine in subjects aged 6-35 months, seroprotection rate of HI antibodies against any subtype of influenza virus in each group. | 56 days | 
| GMT and GMI of HI antibodies | 28 days after receiving two doses of vaccine in subjects aged 6-35 months, GMT and GMI of HI antibodies against any subtype of influenza virus in each group. | 56 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity Events | The proportion of all adverse reactions/events in each group through 30 days after the second dose. The proportion of serious adverse events (SAE) within 6 months after inoculation in each group. | 30 days and 6 months |