Study to Evaluate the Immunogenicity and Safety of 'IL-YANG Quadrivalent Influenza Vaccine Inj.'

Study Overview
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Brief Summary
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This study evaluates the immunogenicity and safety of 'IL-YANG Quadrivalent Influenza Vaccine Inj.' in healthy male and female adults at the age of 19 or older.

Detailed Description
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In this study, only eligible subjects for the study based on the inclusion/exclusion criteria will be randomized to the following stratification groups by age to receive one dose of the test vaccine, comparator 1, or comparator 2. Group A: healthy adults at the age of ≥ 19 and < 65. Group B: healthy adults at the age of ≥ 65. During the study participation, the investigator will assess immunogenicity and safety in subjects. The investigator will perform immunogenicity tests at Visits 1 and 3 (end of study visit) for immunogenicity evaluation (prior to the investigational product vaccination) and instruct subjects to record AEs occurring after the investigational product vaccination for safety assessment. A blood sample will be collected from a subject who is assigned a subject number. Following an intramuscular injection of 0.5mL investigational product in the deltoid muscle of the shoulder, the subject will have a study visit on Week 4 for blood sampling for antibody titer testing. In addition, a telephone visit will be performed to assess serious AEs (SAEs) up to Day 180 after vaccination.

Official Title
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A Multicenter, Randomized, Double-blind, Active-controlled, Parallel Phase III Study to Investigate the Immunogenicity and Safety of 'IL-YANG Quadrivalent Influenza Vaccine Inj.' After Intramuscular Administration in Healthy Adult Subjects

Conditions
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Influenza

Intervention / Treatment
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* Biological: IL-YANG Quadrivalent Influenza Vaccine
* Biological: IL-YANG Flu Vaccine Prefilled Syringe
* Biological: IL-YANG Trivalent Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women at the age of 19 or older. Women of childbearing potential must have a negative pregnancy test (urine HCG) at the screening visit. Subjects who were given, and fully understood, the information about the study, and have provided voluntary written informed consent to participate in the study and to comply with all applicable study requirements. Exclusion Criteria: Subjects with known allergy to eggs, chicken, or any components of the study vaccine. Subjects who had received an influenza vaccine within the last 6 months prior to study entry. Subjects who have immune function disorders including immunodeficiency diseases or relevant family history. Subjects who donated blood within 1 week prior to vaccination or plan to donate blood during the period from Day 1 to Month 7 of vaccination. Subjects with a history of Guillain-Barre syndrome. Subjects with Down's syndrome or cytogenetic disorders. Subjects who are considered by the investigator to have difficulties in study participation due to severe chronic diseases (e.g., cardiovascular diseases except controlled hypertension and respiratory diseases with respiratory failure, metabolic diseases, renal function disorders, hemoglobinopathy, etc.). Subjects with hemophilia or coagulation disorder, who are at increased risk of serious bleeding during intramuscular injection. Subjects who had an acute fever with body temperature > 38.0 ºC within 72 hours prior to administration of the study vaccine. Subjects who had received another vaccine within 28 days before administration of the study vaccine or are planning to receive another vaccine during the study. Subjects who had received immunosuppressants or immune modifying drugs within 3 months prior to the investigational product vaccination. Azathioprine, cyclosporin, interferon, G-CSF, tacrolimus, everolimus, sirolimus, etc. High dose corticosteroids (a subject taking high doses, which is defined as 2mg/kg/day or higher of prednisolone administered for longer than 14 consecutive days, is not eligible for this study. The use of inhaled, nasal and topical corticosteroids is allowed, regardless of doses). Subjects who had previously received immunoglobulin or blood-derived products within the last 3 months prior to administration of the study vaccine, or are scheduled to receive a treatment with blood-derived products during the study. Subjects who had participated in another clinical trial within the 30 days before administration of the study vaccine. Female subjects of childbearing potential who do not agree to use an acceptable method of birth control* for this study during the study period. Medically acceptable methods of birth control: condom, injectable or implantable contraceptives, intrauterine device, or oral contraceptives, etc. Subjects with other clinically significant medical or psychiatric illness who in the investigator's opinion, are not be suitable for the study.

Ages Eligible for Study
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Minimum Age: 19 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IL-YANG Quadrivalent Influenza Vaccine<br>The QIV is included both B strain (Yamagata, Victoria). | Biological: IL-YANG Quadrivalent Influenza Vaccine<br>* A single 0.5mL dose administrated as an intramuscular injection.<br>|
| Active Comparator: IL-YANG Flu Vaccine Prefilled Syringe<br>This TIV is included the B/Yamagata strain, and it was approved for commercial sale by MFDS. | Biological: IL-YANG Flu Vaccine Prefilled Syringe<br>* A single 0.5mL dose administrated as an intramuscular injection.<br>|
| Active Comparator: IL-YANG Trivalent Influenza Vaccine<br>This TIV is included the B/Victoria strain. | Biological: IL-YANG Trivalent Influenza Vaccine<br>* A single 0.5mL dose administrated as an intramuscular injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Healthy Adults Aged ≥19 Years With Seroconversion | Seroconversion is defined as follows. (Case 1) A pre-vaccination (Day 0) HI antibody titer < 1:10 and a post-vaccination (Day 28) HI antibody titer ≥ 1: 40. or (Case 2) a pre-vaccination (Day 0) HI antibody titer ≥ 1:10 and a minimum four-fold rise in post-vaccination (Day 28) HI antibody titer. | Day 28 | 
| Rate of Healthy Adults Aged ≥19 Years With Seroprotection | Seroprotection: A post-vaccination (Day 28) HI antibody titer ≥ 1:40. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With SCR on Day 28 After Vaccination of the Investigational Product by Age Group | The percentage of subjects with HI antibody SCR on Day 28 after vaccination of the investigational product was calculated and its 95% two-sided CI was presented for each strain by treatment group and by age group. The immunogenicity of the test vaccine was to be demonstrated if the lower limit of the 95% two-sided CI by age group was higher than the above mentioned criteria (40% for < 65 years of age, 30% for ≥ 65 years of age) in each treatment group. | Day 28 | 
| Rate of Healthy Adults Aged ≥19   <65 Years and ≥65 Years With Seroprotection, Respectively. | Seroprotection is defined as follows. subjects who have a post-vaccination (Day 28) HI antibody titer ≥ 1: 40 | Day 28 | 
| Geometric Mean Titer as Measured by HI Antibody Titer on Day 28 After Vaccination of the Investigational Product (GMTcomparator/GMTtest Vaccine). |  | Day 28 | 
| Difference of Seroconversion Rate(SCR) of HI Antibody Titer After 28days Vaccination(SCRcomparator-SCRtest Vaccine) | The IL-YANG Quadrivalent Influenza Vaccine contain two types of B strain, while two kinds of Trivalent Influenza Vaccine contain each type of B strain. Primary outcome was about seroconversion and seroprotection rate of HI antibody, so each results of 3 kinds of vaccine was described. Considering the cross-reaction between two types of B strain, the analysis was designed in a way that the SCR/SPR of the B strains can be compared, respectively. However, secondary outcome, unlike the primary outcome, is expressed as a ratio(difference of seroconversion rate). So, the above factors were not to be consider. All methods of analysis are comply with the request of MFDS, and the result data that may make you confuse will be delete. | Day 28 | 
| Geometric Mean Titer as Measured by HI Antibody Titer Before (Day 0) and on Day 28 After Vaccination of the Investigational Product. |  | Day 28 | 
| Geometric Mean Ratio as Measured by HI Antibody Titer Before (Day 0) and on Day 28 After Vaccination of the Investigational Product. |  | Day 28 |