Seasonal Influenza
Conditions
Keywords
seasonal influenza, vaccine
Brief summary
This study will evaluate the safety and immunogenicity in healthy children and adolescents after one or two IM dose(s) of trivalent subunit inactivated flu vaccine.
Interventions
BIOLOGICALTIV
Investigational egg-derived trivalent subunit influenza vaccine.
BIOLOGICALTIVf
US licensed trivalent inactivated subunit influenza vaccine -Fluvirin (Novartis Vaccines and Diagnostics) is approved for use in subjects ≥4 years.
BIOLOGICALComparator TIV
US licensed trivalent subunit inactivated influenza vaccine- Fluzone (Sanofi Pasteur) is approved for use in children \<4 years.
Sponsors
Novartis Vaccines
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
* Males and females aged 3 to 17 years, in good health as determined by medical history, physical examination and clinical judgment of the investigator * Documented consent provided by parents or legal guardians * For individuals 8 years of age and older, informed assent to participate in the study after the nature of the study had been explained to them in terms they could understand * Individuals and parents/guardians who were able to comply with all study procedures and were available for all clinic visits scheduled in the study
Exclusion criteria
* Parents or legal guardians and individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study * Parents or legal guardians and individuals providing assent who do not consent to the retention of the subject's serum samples after study completion * Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may have interfered with the subject's ability to participate in the study * Individuals with history or any illness that, in the opinion of the investigator, might have interfered with the results of the study or posed additional risk to the subjects due to participation in the study * History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, latex, to any excipients, and to eggs (including ovalbumin), chicken protein, influenza viral protein, kanamycin, neomycin sulphate, cetyltrimethylammonium bromide (CTAB), polysorbate 80, neomycin, polymixin, formaldehyde, thimerosal, beta propiolactone, or nonoxynol-9 * History of any serious disease, such as: 1. cancer 2. history of serious chronic, rheumatologic, neurologic and hematologic diseases 3. history of underlying medical condition such as inborn errors of metabolism * Known or suspected impairment/alteration of immune function, including: 1. chronic use of oral steroids within 60 days prior to Visit 1 (use of inhaled, intranasal, or topical corticosteroids is allowed) 2. receipt of immunostimulants within 60 days prior to Visit 1 3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study 4. HIV infection or HIV-related disease * Pregnant or breast-feeding female and any positive or indeterminate pregnancy test * Received an influenza vaccine within 6 months prior to Visit 1 * Laboratory-confirmed or suspected influenza disease within 6 months prior to Visit 1 * Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study * Experienced a fever and/or any acute illness within 3 days prior to each study vaccination
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | Day 22 for non-naive/Day 50 for naive subjects | The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer \<1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer |
| Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 for non-naive/Day 50 for naive subjects | The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1, Day 29, and Day 50 | The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers ≥40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50). This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%, for each vaccine strain. |
| Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 and Day 50 | The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50). This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is ≥40, for each vaccine strain. |
| Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 for non-naive/Day 50 for naive subjects | The percentages of 3 to 8 year old subjects achieving HI titers ≥40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported. This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40, is ≥70%. |
| Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Day 1 to 180 (non-naive )/Day 1 to 209 (naive) | The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported. |
| Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Day 1 to 7 after vaccination | The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported. |
| Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | Day 22 for non-naive/Day 50 for naive | The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported. This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is ≥40. |
Countries
Colombia, Mexico, Panama, Philippines
Participant flow
Recruitment details
The study was conducted in 13 centers across 4 countries: Mexico, Colombia, Panama and Philippines.
Pre-assignment details
Due to GCP non-compliance at the Mexico site, data of 312 subjects (3-8 year olds) enrolled from this site were excluded from the final immunogenicity and safety analysis. The population was analyzed in the enrolled set.
Participants by arm
| Arm | Count |
|---|---|
| TIV (3-8 Years) The group consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). The non-naive subjects received one dose and naive subjects received two doses of investigational TIV. | 1,042 |
| Control (3-8 Years) The group \[control (4-8 years) + control (3 to\<4 years)\] consisted of naive (who have never received influenza vaccination or had received only one influenza vaccine dose in the same season) and non-naive subjects (who had a record of previous influenza vaccination). Subjects (4-\<9 years) received TIVf and subjects (3-\<4 years) received comparator TIV. The non-naive subjects received one dose and naive subjects received two doses of vaccine. | 533 |
| TIV (9-17 Years) All subjects received one dose of investigational TIV. | 817 |
| Control (9-17 Years) All subjects received one dose of control TIV (eTIV\_f). | 412 |
| Total | 2,804 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Inappropriate enrollment | 0 | 2 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 17 | 12 | 3 | 9 | 4 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 9 | 2 | 1 | 1 | 0 |
Baseline characteristics
| Characteristic | TIV (3-8 Years) | Control (3-8 Years) | TIV (9-17 Years) | Control (9-17 Years) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 5.6 years STANDARD_DEVIATION 1.6 | 5.6 years STANDARD_DEVIATION 1.6 | 12.4 years STANDARD_DEVIATION 2.4 | 12.3 years STANDARD_DEVIATION 2.3 | 8.6 years STANDARD_DEVIATION 3.9 |
| Sex: Female, Male Female | 517 Participants | 269 Participants | 398 Participants | 215 Participants | 1399 Participants |
| Sex: Female, Male Male | 525 Participants | 264 Participants | 419 Participants | 197 Participants | 1405 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 657 / 1,039 | 342 / 531 | 385 / 817 | 196 / 412 |
| serious Total, serious adverse events | 14 / 1,039 | 3 / 531 | 4 / 817 | 3 / 412 |
Outcome results
Primary
Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs)
The non-inferiority of the antibody responses of investigational TIV compared to control vaccine assessed in terms of post vaccination GMTs, at 21 days after last vaccination against the three homologous vaccine strains in 3 to 8 year old children.
Time frame: Day 22 for non-naive/Day 50 for naive subjects
Population: Analysis was performed on the per protocol population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (H1N1 strain, N=917,467) | 26 Titers |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (H1N1 strain,N=917,468) | 1157 Titers |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (H3N2 strain) | 142 Titers |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (H3N2 strain, N=917,468) | 1385 Titers |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (B strain) | 12 Titers |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (B strain) | 208 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (B strain) | 13 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (H1N1 strain, N=917,467) | 28 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (H3N2 strain, N=917,468) | 2032 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (H1N1 strain,N=917,468) | 1501 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Day 22 or Day 50 (B strain) | 195 Titers |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of Post Vaccination Geometric Mean Titers (GMTs) | Baseline (H3N2 strain) | 150 Titers |
Comparison: Non-inferiority of investigational TIV to licensed control TIV against A/H1N1 influenza strain95% CI: [1.11, 1.56]
Comparison: Non-inferiority of investigational TIV to licensed control TIV against A/H3N2 influenza strain95% CI: [1.34, 1.64]
Comparison: Non-inferiority of investigational TIV to licensed control TIV against B influenza strain95% CI: [0.85, 1.07]
Primary
Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion
The non-inferiority of the antibody responses of investigational TIV compared to control TIV assessed in terms of the percentage of subjects achieving seroconversion, against the three homologous vaccine strains,in children 3 to 8 years of age, at 21 days after last vaccination. Seroconversion was defined as a pre-vaccination haemagglutinin inhibition (HI) titer \<1:10 and post-vaccination HI titer ≥1:40 or as a pre-vaccination HI titer ≥1:10 and at minimum four-fold rise in post-vaccination antibody titer
Time frame: Day 22 for non-naive/Day 50 for naive subjects
Population: Analysis was done on per protocol population i.e-all subjects who correctly received study vaccinations,provided evaluable serum samples at the relevant time points, and had no major protocol violation as defined prior to unblinding.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | H1N1 strain (N=916,467) | 95 Percentages |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | H3N2 strain (N=917,468) | 78 Percentages |
| TIV (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | B strain | 87 Percentages |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | H1N1 strain (N=916,467) | 94 Percentages |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | H3N2 strain (N=917,468) | 87 Percentages |
| Control (3-8 Years) | Comparison of Antibody Responses of Investigational TIV to Control Vaccine in Terms of the Percentage of Subjects Achieving Seroconversion | B strain | 85 Percentages |
Comparison: Non-inferiority of investigational TIV to control TIV against A/H1N1 influenza strain95% CI: [-4, 2]
Comparison: Non-inferiority of investigational TIV to control TIV against A/H3N2 influenza strain95% CI: [6, 14]
Comparison: Non-inferiority of investigational TIV to the control TIV against B influenza strain95% CI: [-5, 3]
Secondary
Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine
The number of 3-17 year old children with solicited local and systemic adverse events and other adverse events, after receiving either one or two doses of investigational TIV as compared to control vaccine are reported.
Time frame: Day 1 to 7 after vaccination
Population: Analysis was done on the safety set population i.e all subjects who received at least one study vaccine and provided post vaccination safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Myalgia | 78 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fatigue | 34 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Arthralgia | 41 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Headache (N=1037,531,817,411) | 101 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Sweating | 37 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site erythema | 1 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Analgesic/Antipyretic med.used(N=1032,531,816,412) | 91 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site induration | 10 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site pain | 363 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site swelling | 11 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Other | 153 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any systemic | 262 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any local | 364 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Chills | 37 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Stayed at home due to reaction(N=1019,524,809,411) | 93 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fever (≥ 38°C) | 116 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Malaise | 77 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site ecchymosis | 1 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fatigue | 22 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Myalgia | 50 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site ecchymosis | 1 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Other | 89 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fever (≥ 38°C) | 68 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Arthralgia | 20 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any local | 216 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Sweating | 29 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site swelling | 11 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Headache (N=1037,531,817,411) | 52 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Analgesic/Antipyretic med.used(N=1032,531,816,412) | 52 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site pain | 215 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Malaise | 51 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site erythema | 1 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Stayed at home due to reaction(N=1019,524,809,411) | 54 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Chills | 20 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any systemic | 161 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site induration | 6 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Other | 103 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site pain | 268 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site ecchymosis | 2 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site erythema | 2 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site induration | 5 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site swelling | 6 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any systemic | 193 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Chills | 38 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Malaise | 68 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Myalgia | 54 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Arthralgia | 26 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Headache (N=1037,531,817,411) | 93 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Sweating | 43 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fatigue | 52 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fever (≥ 38°C) | 39 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any local | 270 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Analgesic/Antipyretic med.used(N=1032,531,816,412) | 22 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Stayed at home due to reaction(N=1019,524,809,411) | 89 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Analgesic/Antipyretic med.used(N=1032,531,816,412) | 9 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fatigue | 21 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Chills | 8 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any systemic | 94 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site pain | 146 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Fever (≥ 38°C) | 12 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site swelling | 3 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site induration | 6 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any local | 148 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Other | 54 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site erythema | 1 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Injection site ecchymosis | 0 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Headache (N=1037,531,817,411) | 38 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Arthralgia | 12 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Stayed at home due to reaction(N=1019,524,809,411) | 49 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Sweating | 22 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Myalgia | 34 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Solicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Malaise | 27 Subjects |
Secondary
Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine
The number of 3-17 year old children reporting any unsolicited adverse event and any serious adverse event (SAE) after receiving either one or two doses of investigational TIV and control vaccine are reported.
Time frame: Day 1 to 180 (non-naive )/Day 1 to 209 (naive)
Population: Analysis was done on the safety set population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any adverse event | 395 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related adverse event | 64 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Serious adverse event | 14 Subjects |
| TIV (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related serious adverse event | 1 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related adverse event | 36 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Serious adverse event | 3 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related serious adverse event | 0 Subjects |
| Control (3-8 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any adverse event | 194 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Serious adverse event | 4 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related adverse event | 23 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related serious adverse event | 0 Subjects |
| TIV (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any adverse event | 101 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related serious adverse event | 0 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | At least possibly related adverse event | 11 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Any adverse event | 58 Subjects |
| Control (9-17 Years) | Number of Subjects Reporting Unsolicited Adverse Events After Vaccination With Investigational TIV and Control Vaccine | Serious adverse event | 3 Subjects |
Secondary
Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine.
The percentages of 3 to 8 year old subjects achieving HI titers ≥40 after receiving either one or two doses of investigational TIV or control vaccine, 21 days after last vaccination, are reported. This criterion according to the US (CBER)guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40, is ≥70%.
Time frame: Day 22 for non-naive/Day 50 for naive subjects
Population: Analysis was performed on per protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (H1N1strain, N=917,467) | 49 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (H1N1strain; N=917,468) | 97 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (H3N2 strain) | 84 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (H3N2 strain; N=917,468) | 100 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (B strain) | 23 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (B strain) | 95 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (B strain) | 26 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (H1N1strain, N=917,467) | 48 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (H3N2 strain; N=917,468) | 100 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (H1N1strain; N=917,468) | 95 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Day 22 or Day 50 (B strain) | 92 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects Achieving HI Titers ≥40 Following Vaccination With Investigational TIV or Control Vaccine. | Baseline (H3N2 strain) | 85 Percentages of subjects |
Secondary
Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine
The percentages of 3 to 8 years-old subjects achieving seroconversion in HI antibody titers after receiving either one or two doses of investigational TIV or control vaccine, at 21 days after last vaccination, are reported. This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 22 and day 50 (21 days after last vaccination) is ≥40.
Time frame: Day 22 for non-naive/Day 50 for naive
Population: Analysis was performed on the per protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | H1N1 strain (N= 916,467) | 95 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | H3N2 strain ( N= 917,468) | 78 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | B strain | 87 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | H1N1 strain (N= 916,467) | 94 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | H3N2 strain ( N= 917,468) | 87 Percentages of subjects |
| Control (3-8 Years) | Percentages of Subjects With Seroconversion in Antibody Titers Following Vaccination With Investigational TIV or Control Vaccine | B strain | 85 Percentages of subjects |
Secondary
Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine.
The percentage of 3 to 8 years-old vaccine-naive subjects achieving HI titers ≥40, after receiving two doses of investigational TIV or control vaccine. The time frame of evaluation was 28 days after first (Day 29) and 21 days after second vaccine dose (Day 50). This criterion according to the US (CBER) guideline is met if the lower bound of the two sided 95%CI for percentage of subjects achieving HI titers ≥40 is ≥70%, for each vaccine strain.
Time frame: Day 1, Day 29, and Day 50
Population: Analysis was done on the per protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (B strain) | 98 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (H3N2 strain) | 88 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (H1N1 strain, N=819,413) | 83 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (H3N2 strain, N= 819, 413) | 99 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (H1N1 strain, N=819,412) | 49 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (H3N2 strain,N= 819, 413) | 100 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (H1N1 strain, N= 819,413) | 99 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (B strain) | 25 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (B strain, N= 820,412) | 82 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (B strain) | 26 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (B strain, N= 820,412) | 81 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (B strain) | 94 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (H1N1 strain, N=819,412) | 48 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (H1N1 strain, N=819,413) | 82 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (H1N1 strain, N= 819,413) | 98 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 1 (H3N2 strain) | 90 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 29 (H3N2 strain, N= 819, 413) | 98 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving HI Titers ≥40 After Receiving Two Doses of Investigational TIV or Control Vaccine. | Day 50 (H3N2 strain,N= 819, 413) | 100 Percentages of subjects |
Secondary
Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine
The percentages of 3 to 8 years-old vaccine naive children achieving seroconversion or significant increase in HI antibody titers after receiving two doses of investigational TIV or control vaccine, are reported. The time frame of evaluation was 28 days after first (Day 29) and 21 days after the second dose (Day 50). This criterion, according to the US (CBER) guideline, is met if the lower limit of 95% CI of percentage of subjects achieving seroconversion or significant increase at day 29 and day 50 is ≥40, for each vaccine strain.
Time frame: Day 29 and Day 50
Population: Analysis was done on the per protocol population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (H1N1 strain, N= 818,412) | 82 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (H1N1 strain, N= 818,412) | 98 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (H3N2 strain, N= 819,413) | 74 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (H3N2 strain, N= 819,413) | 78 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (B strain, N= 820,412) | 74 Percentages of subjects |
| TIV (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (B strain) | 89 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (B strain, N= 820,412) | 73 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (H1N1 strain, N= 818,412) | 81 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (H3N2 strain, N= 819,413) | 87 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (H1N1 strain, N= 818,412) | 96 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 50 (B strain) | 88 Percentages of subjects |
| Control (3-8 Years) | Percentages of Vaccine-naive Children Achieving Seroconversion in Antibody Titers, After Receiving Two Doses of Investigational TIV or Control Vaccine | Day 29 (H3N2 strain, N= 819,413) | 87 Percentages of subjects |