Healthy
Conditions
Keywords
Influenza, Influenza vaccine, Split influenza vaccine, Seasonal influenza vaccine
Brief summary
The purpose of this study is to evaluate the safety and immunogenicity of IL-YANG Inactivated Split Influenza Vaccine (IL-YANG FLU Vaccine Prefilled Syringe INJ.) administered as a single intramuscular injection.
Detailed description
This was a multi-center, randomized, double-blind, active-controlled study. Before initiation of any protocol-specific activities, written informed consent was obtained from each patient and their legally acceptable representatives (consent of the legally acceptable representative was required for children younger than 10 years of age, and for the some sites, for children younger than 7 years of age). Subjects who met all of the eligibility criteria after screening assessments as specified in the protocol, were randomized into the test group or the comparator group in a ratio of 5 to 1 according to the pre-generated site-specific randomization table, and received a single dose or two doses of the study vaccine. The investigator performed the efficacy (immunogenicity) and safety assessments throughout the study. Efficacy data were collected at Visit 1 (prior to vaccination) and at the end-of-study visit for efficacy (immunogenicity) assessments, and for safety assessment, subjects and their legally acceptable representatives were instructed to record any treatment-emergent adverse event in Patient Diary cards. For all randomized subjects, blood sample was obtained prior to vaccination, and the study vaccine 0.5mL or 0.25mL was administered to the deltoid muscle or anterolateral thigh muscle. For children aged from 6 months to \<9 years of age who had not been previously exposed to influenza virus or had not previously received influenza vaccine, another dose of the study vaccine was administered 4 to 5 weeks after the first dose. Blood samples were collected 4 to 5 weeks after the last dose of the study drug for the assessment of antibody titer. All subjects were followed for 6 months after the last dose of the study drug for the safety assessments, and Month 6 follow-up visit was the end-of-study visit.
Interventions
IL-YANG FLU Vaccine Prefilled Syringe INJ.0.5mL or 0.25mL
BIOLOGICALVAXIGRIP Prefilled Syringe INJ.
VAXIGRIP Prefilled Syringe INJ.0.5mL or 0.25mL
Sponsors
Il-Yang Pharm. Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Months to 18 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy men or women aged from 6 months to \< 18 years * Subjects were born after full term pregnancy (37 weeks) * Voluntary written informed consent was obtained from the subject and the subject's legally acceptable representative (consent of legally acceptable representative was required for subjects younger than 10 years of age (and for subjects younger than 7 years of age for the some institutions)).
Exclusion criteria
* Subject with a known allergy to eggs, chicken, neomycin, gentamicin or any components of the study vaccine * Subject who had received an influenza vaccine within the last 6 months * Subject who has, or has a family history of, an immune system disorder including immune deficiency disease * Subject with a history of Guillain-Barre syndrome * Subject with Down's syndrome or cytogenetic disorders. * Subject with severe chronic disease which in the investigator's opinion would not make the subject a good candidate for the clinical trial * Subject with hemophilia or being treated with an anticoagulant, who are at increased risk of serious bleeding during intramuscular injection * Subject who had an acute fever with body temperature \> 38.0 Cº within 72 hours prior to administration of the study vaccine * Subject who had previously received another vaccine within 28 days before administration of the study drug, or is scheduled to receive another vaccine during the study period. * Subject who had received immunosuppressant or immune modifying drug within the last 3 months prior to administration of the study vaccine * Subject who had previously received immunoglobulin or blood-derived products within the last 3 months prior to administration of the study vaccine, or is expecting to be treated with immunoglobulin or blood-derived products during the study. * Subject who had participated in another experimental study within 30 days prior to administration of the study vaccine * Subject with other clinically significant medical or psychological condition who in the investigator's opinion would not be suitable for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | up to Day28(+7) | 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. |
| Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | up to Day28(+7) | Seroconversion: a pre-vaccination (Day 0) hemagglutination-inhibition (HI) antibody titer \< 1:10 and a post-vaccination (last vaccination + Day 28) HI antibody titer ≥ 1: 40 (Case 1), or a pre-vaccination (Day 0) HI antibody titer ≥ 1:10 and a minimum four-fold rise in post-vaccination (last vaccination + Day 28) HI antibody titer (Case 2), |
| Seroprotection Rate for HI Antibody | up to Day28(+7) | Percentage of Participants With Healthy Children Aged From 6 Months to \<18 Years With Seroprotection |
| Seroprotection Rate of HI Antibody | up to Day28(+7) | Percentage of subjects achieving seroprotection for HI antibody after administration of the study vaccine depending of the number of vaccination |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMR of HI Antibody Titer Before Vaccination and After Vaccination | Day28(+7) | Geometric Mean Ratio (GMR), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer. |
| Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Day28(+7) | — |
| Geometric Mean Titer* (GMT) of HI Antibody | Day28(+7) | Geometric Mean Titer (GMT), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| IL-YANG PFS IL-YANG FLU Vaccine Prefilled Syringe INJ.
IL-YANG FLU Vaccine Prefilled Syringe INJ.: IL-YANG FLU Vaccine Prefilled Syringe INJ.0.5mL or 0.25mL | 347 |
| TIV PFS VAXIGRIP Prefilled Syringe INJ.
VAXIGRIP Prefilled Syringe INJ.: VAXIGRIP Prefilled Syringe INJ.0.5mL or 0.25mL | 69 |
| Total | 416 |
Baseline characteristics
| Characteristic | IL-YANG PFS | TIV PFS | Total |
|---|---|---|---|
| Age, Continuous | 7.83 years STANDARD_DEVIATION 4.87 | 7.45 years STANDARD_DEVIATION 5.01 | 7.77 years STANDARD_DEVIATION 4.89 |
| Sex: Female, Male Female | 191 Participants | 34 Participants | 225 Participants |
| Sex: Female, Male Male | 156 Participants | 35 Participants | 191 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 185 / 347 | 41 / 69 |
| serious Total, serious adverse events | 8 / 347 | 0 / 69 |
Outcome results
Primary
Percentage of Participants With Healthy Children Aged From 6 Months to <18 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.
Time frame: up to Day28(+7)
Population: Whole participant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-YANG PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain H1N1 | 62.02 percentage of paticipants |
| IL-YANG PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain H3N2 | 53.41 percentage of paticipants |
| IL-YANG PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain B | 54.90 percentage of paticipants |
| TIV PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain H1N1 | 76.81 percentage of paticipants |
| TIV PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain H3N2 | 57.35 percentage of paticipants |
| TIV PFS | Percentage of Participants With Healthy Children Aged From 6 Months to <18 Years With Seroconversion | Strain B | 66.18 percentage of paticipants |
Primary
Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination
Seroconversion: a pre-vaccination (Day 0) hemagglutination-inhibition (HI) antibody titer \< 1:10 and a post-vaccination (last vaccination + Day 28) HI antibody titer ≥ 1: 40 (Case 1), or a pre-vaccination (Day 0) HI antibody titer ≥ 1:10 and a minimum four-fold rise in post-vaccination (last vaccination + Day 28) HI antibody titer (Case 2),
Time frame: up to Day28(+7)
Population: This is because the results showed that the seroconversion rate of HI antibody varies depending on the number of vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H1N1(1st) | 60.06 percentage of participants |
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H1N1(2nd) | 82.76 percentage of participants |
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H3N2(1st) | 53.41 percentage of participants |
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H3N2(2nd) | 75.86 percentage of participants |
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain B(1st) | 54.22 percentage of participants |
| IL-YANG PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain B(2nd) | 62.07 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain B(1st) | 66.13 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H1N1(1st) | 54.84 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H3N2(2nd) | 66.67 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H1N1(2nd) | 66.67 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain B(2nd) | 66.67 percentage of participants |
| TIV PFS | Percentage of Subjects Achieving Seroconversion for HI Antibody After Administration of the Study Vaccine Depending of the Number of Vaccination | Strain H3N2(1st) | 56.45 percentage of participants |
Primary
Seroprotection Rate for HI Antibody
Percentage of Participants With Healthy Children Aged From 6 Months to \<18 Years With Seroprotection
Time frame: up to Day28(+7)
Population: Whole participant
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-YANG PFS | Seroprotection Rate for HI Antibody | Strain H1N1 | 94.96 percentage of paticipants |
| IL-YANG PFS | Seroprotection Rate for HI Antibody | Strain H3N2 | 93.77 percentage of paticipants |
| IL-YANG PFS | Seroprotection Rate for HI Antibody | Strain B | 95.25 percentage of paticipants |
| TIV PFS | Seroprotection Rate for HI Antibody | Strain H1N1 | 89.71 percentage of paticipants |
| TIV PFS | Seroprotection Rate for HI Antibody | Strain H3N2 | 91.18 percentage of paticipants |
| TIV PFS | Seroprotection Rate for HI Antibody | Strain B | 95.59 percentage of paticipants |
Primary
Seroprotection Rate of HI Antibody
Percentage of subjects achieving seroprotection for HI antibody after administration of the study vaccine depending of the number of vaccination
Time frame: up to Day28(+7)
Population: This is because the results showed that the seroconversion rate of HI antibody varies depending on the number of vaccination.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain H1N1(1st) | 96.10 percentage of participants |
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain H1N1(2nd) | 82.76 percentage of participants |
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain H3N2(1st) | 95.45 percentage of participants |
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain H3N2(2nd) | 75.86 percentage of participants |
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain B(1st) | 96.75 percentage of participants |
| IL-YANG PFS | Seroprotection Rate of HI Antibody | Strain B(2nd) | 79.31 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain B(1st) | 96.77 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain H1N1(1st) | 91.94 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain H3N2(2nd) | 66.67 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain H1N1(2nd) | 66.67 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain B(2nd) | 83.33 percentage of participants |
| TIV PFS | Seroprotection Rate of HI Antibody | Strain H3N2(1st) | 93.55 percentage of participants |
Secondary
Geometric Mean Titer* (GMT) of HI Antibody
Geometric Mean Titer (GMT), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer.
Time frame: Day28(+7)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H3N2(pre) | 31.85 Titer |
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H1N1(pre) | 24.40 Titer |
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H1N1(post) | 111.40 Titer |
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H3N2(post) | 110.60 Titer |
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain B(pre) | 36.22 Titer |
| IL-YANG PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain B(post) | 130.53 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain B(pre) | 39.44 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H3N2(pre) | 30.00 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H3N2(post) | 104.92 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H1N1(pre) | 24.80 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain B(post) | 151.70 Titer |
| TIV PFS | Geometric Mean Titer* (GMT) of HI Antibody | Strain H1N1(post) | 88.45 Titer |
Secondary
GMR of HI Antibody Titer Before Vaccination and After Vaccination
Geometric Mean Ratio (GMR), as measured by pre-vaccination (Day 0) HI antibody titer and post-vaccination (vaccination + 28 days) HI antibody titer.
Time frame: Day28(+7)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| IL-YANG PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain H1N1 | 4.57 Ratio of GMT titer |
| IL-YANG PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain H3N2 | 3.47 Ratio of GMT titer |
| IL-YANG PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain B | 3.60 Ratio of GMT titer |
| TIV PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain H1N1 | 3.57 Ratio of GMT titer |
| TIV PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain H3N2 | 3.50 Ratio of GMT titer |
| TIV PFS | GMR of HI Antibody Titer Before Vaccination and After Vaccination | Strain B | 3.85 Ratio of GMT titer |
Secondary
Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer
Time frame: Day28(+7)
Population: Number of subjects whose HI antibody titer increased minimum four-fold on day 28 after vaccination
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| IL-YANG PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain H1N1 | 35.29 percentage of participants |
| IL-YANG PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain H3N2 | 61.90 percentage of participants |
| IL-YANG PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain B | 18.75 percentage of participants |
| TIV PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain H1N1 | 28.57 percentage of participants |
| TIV PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain H3N2 | 50.00 percentage of participants |
| TIV PFS | Number of Subjects With a Pre-vaccination (Day 0) HI Antibody Titer < 1:40, Minimum Four-fold Rise in Post-vaccination (Day 28) HI Antibody Titer | Strain B | 0.00 percentage of participants |