Trial Outcomes & Findings for Safety and Immunogenicity of Three Influenza Vaccines in Children Aged 4 Years Old to Less Than 18 Years Old (NCT NCT01992107)

NCT ID: NCT01992107

Last Updated: 2015-12-08

Results Overview

Immunogenicity of QIVc to comparator TIV1c (For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c) was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by hemagglutination inhibition (HI) assay, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c. Non-inferiority was established if the upper bound of the two-sided 95% confidence interval (CI) for the ratio of GMTs (GMT TIV1c or TIV2c /GMT QIVc) for HI antibody does not exceed the non-inferiority margin of 1.5.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2333 participants

Primary outcome timeframe

Day 1,Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Results posted on

2015-12-08

Participant Flow

Subjects were recruited from 90 centers in the United States (US)

All enrolled subjects were included in the trial

Participant milestones

Participant milestones
Measure	QIVc Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Overall Study STARTED	1159	593	581
Overall Study COMPLETED	1091	560	545
Overall Study NOT COMPLETED	68	33	36

Reasons for withdrawal

Reasons for withdrawal
Measure	QIVc Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Overall Study Administrative reasons	2	0	0
Overall Study Adverse Event	0	1	0
Overall Study Lost to Follow-up	46	22	26
Overall Study noncompliance and were unavailable	7	3	2
Overall Study Withdrawal by Subject	13	7	8

Baseline Characteristics

Safety and Immunogenicity of Three Influenza Vaccines in Children Aged 4 Years Old to Less Than 18 Years Old

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QIVc n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	Total n=2333 Participants Total of all reporting groups
Age, Continuous	9.5 year STANDARD_DEVIATION 3.8 • n=5 Participants	9.5 year STANDARD_DEVIATION 3.8 • n=7 Participants	9.3 year STANDARD_DEVIATION 3.7 • n=5 Participants	9.5 year STANDARD_DEVIATION 3.8 • n=4 Participants
Sex: Female, Male Female	556 Participants n=5 Participants	284 Participants n=7 Participants	284 Participants n=5 Participants	1124 Participants n=4 Participants
Sex: Female, Male Male	603 Participants n=5 Participants	309 Participants n=7 Participants	297 Participants n=5 Participants	1209 Participants n=4 Participants

PRIMARY outcome

Timeframe: Day 1,Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on Per Protocol (PP) Population i.e. all subjects in the Full Analysis Set (FAS) efficacy/immunogenicity population correctly received the vaccine, had no major protocol deviations leading to exclusion as defined prior to unblinding/analysis and are not excluded due to other reasons defined prior to unblinding or analysis

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c B2: Day 22/Day 50 (N=1009, 501)	185 Titers Interval 171.0 to 200.0	NA Titers Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	185 Titers Interval 166.0 to 207.0	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c A/H1N1: Day 1 (N=1014, 510)	96 Titers Interval 86.0 to 107.0	100 Titers Interval 86.0 to 116.0	NA Titers Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c A/H1N1: Day 22/Day 50 (N=1014, 510)	1090 Titers Interval 1027.0 to 1157.0	1125 Titers Interval 1034.0 to 1224.0	NA Titers Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c A/H3N2: Day 1 (N=1013, 510)	206 Titers Interval 188.0 to 225.0	196 Titers Interval 172.0 to 222.0	NA Titers Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c A/H3N2: Day 22/Day 50 (N=1013, 510)	738 Titers Interval 703.0 to 774.0	776 Titers Interval 725.0 to 831.0	NA Titers Interval to 0.0 Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c B1: Day 1 (N=1013, 510)	26 Titers Interval 24.0 to 28.0	23 Titers Interval 21.0 to 26.0	NA Titers Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c B1: Day 22/Day 50 (N=1013, 510)	155 Titers Interval 146.0 to 165.0	154 Titers Interval 141.0 to 168.0	NA Titers Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Titre (GMT) in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c or TIV2c B2: Day 1(N=1009, 501)	23 Titers Interval 21.0 to 25.0	NA Titers Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	23 Titers Interval 21.0 to 26.0	—	—	—	—	—	—	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on PP population

Immunogenicity of QIVc to comparator TIVc (For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c) was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase (at least a 4-fold increase in HI titer in subjects seropositive at baseline \[i.e., HI titer ≥1:10 at Day 1\] ) in HI antibody titers, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c Seroconversion was defined in subjects seronegative at baseline (i.e., HI titer \<1:10 at Day 1) as postvaccination HI titer ≥1:40, and defined in subjects seropositive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer.

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c B2: Day 22/Day 50 (N=1009,501)	73 percentages of subjects Interval 70.0 to 76.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	71 percentages of subjects Interval 67.0 to 75.0	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c A/H1N1: Day 22/Day 50 (N=1014,510)	72 percentages of subjects Interval 69.0 to 75.0	75 percentages of subjects Interval 70.0 to 78.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c A/H3N2: Day 22/Day 50 (N=1013, 510)	47 percentages of subjects Interval 44.0 to 50.0	51 percentages of subjects Interval 46.0 to 55.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c B1: Day 22/Day 50 (N=1013,510)	66 percentages of subjects Interval 63.0 to 69.0	66 percentages of subjects Interval 62.0 to 70.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on Full Analysis Set (FAS) immunogenicity set i.e. all subjects in the enrolled set who received ▫ Received at least one study vaccination and provided immunogenicity data at day 1 and day 22 (day 50 for not previously vaccinated subjects)

Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c Seroconversion was defined in subjects seronegative at baseline (i.e., HI titer \<1:10 at Day 1) as postvaccination HI titer ≥1:40, and defined in subjects seropositive at baseline (i.e., HI titer ≥1:10 at Day 1) as a minimum of a 4-fold increase in post-vaccination HI titer. The Center for Biologics Evaluation, Research, and Review (CBER) criterion for an adult population is that the lower bound of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40%

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 22 or Day 50 (N=1113,566)	73 percentages of subjects Interval 70.0 to 76.0	74 percentages of subjects Interval 70.0 to 77.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 22 or Day 50 (N=1108,556)	73 percentages of subjects Interval 70.0 to 76.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	72 percentages of subjects Interval 68.0 to 76.0	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 22 or Day 50 (N=1112,566)	47 percentages of subjects Interval 44.0 to 50.0	51 percentages of subjects Interval 47.0 to 55.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 22 or Day 50 (N=1112,566)	67 percentages of subjects Interval 64.0 to 70.0	66 percentages of subjects Interval 61.0 to 69.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS immunogenicity set (FAS) i.e. all subjects in the enrolled set who received at least one study vaccination and provided immunogenicity data at day 22 (day 50 for not previously vaccinated subjects)

Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing HI titer ≥1:40, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c. The CBER criterion for adult population was that the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 1(N=1113,566)	76 percentages of subjects Interval 73.0 to 78.0	79 percentages of subjects Interval 75.0 to 82.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 22 or Day 50(N=1113,566)	99 percentages of subjects Interval 98.0 to 100.0	99 percentages of subjects Interval 98.0 to 100.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 1(N=1112,566)	90 percentages of subjects Interval 88.0 to 91.0	89 percentages of subjects Interval 86.0 to 92.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 22 or Day 50(N=1112,566)	100 percentages of subjects Interval 99.0 to 100.0	99 percentages of subjects Interval 98.0 to 100.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 1(N=1112,566)	49 percentages of subjects Interval 46.0 to 52.0	45 percentages of subjects Interval 41.0 to 49.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 22 or Day 50(N=1112,566)	92 percentages of subjects Interval 91.0 to 94.0	93 percentages of subjects Interval 90.0 to 95.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 1(N=1108,556)	46 percentages of subjects Interval 43.0 to 49.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	47 percentages of subjects Interval 43.0 to 51.0	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 22 or Day 50(N=1108,556)	91 percentages of subjects Interval 89.0 to 93.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	91 percentages of subjects Interval 88.0 to 93.0	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS immunogenicity set

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 22/Day 50(N=1113,566)	73 percentages of subjects Interval 70.0 to 76.0	74 percentages of subjects Interval 70.0 to 77.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 22/Day 50(N=1112,566)	47 percentages of subjects Interval 44.0 to 50.0	51 percentages of subjects Interval 47.0 to 55.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 22/Day 50(N=1112,566)	67 percentages of subjects Interval 64.0 to 70.0	66 percentages of subjects Interval 61.0 to 69.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 22/Day 50(N=1108,556)	73 percentages of subjects Interval 70.0 to 76.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	72 percentages of subjects Interval 68.0 to 76.0	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS immunogenicity set

Immunogenicity was assessed in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing HI titer ≥1:40, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c The Committee for Medicinal Products for Human Use (CHMP) criterion for an adult population was that the percentage of subjects achieving an HI titer ≥1:40 is \>70%

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 1(N=1113,566)	76 percentages of subjects Interval 73.0 to 78.0	79 percentages of subjects Interval 75.0 to 82.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H1N1: Day 22/Day 50(N=1113,566)	99 percentages of subjects Interval 98.0 to 100.0	99 percentages of subjects Interval 98.0 to 100.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 1(N=1112,566)	90 percentages of subjects Interval 88.0 to 91.0	89 percentages of subjects Interval 86.0 to 92.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years A/H3N2: Day 22/Day 50(N=1112,566)	100 percentages of subjects Interval 99.0 to 100.0	99 percentages of subjects Interval 98.0 to 100.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 1(N=1112,566)	49 percentages of subjects Interval 46.0 to 52.0	45 percentages of subjects Interval 41.0 to 49.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B1: Day 22/Day 50(N=1112,566)	92 percentages of subjects Interval 91.0 to 94.0	93 percentages of subjects Interval 90.0 to 95.0	NA percentages of subjects Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 1(N=1108,556)	46 percentages of subjects Interval 43.0 to 49.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	47 percentages of subjects Interval 43.0 to 51.0	—	—	—	—	—	—	—	—	—	—	—	—
Percentages of Subjects Achieving HI Titer ≥1:40 After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years B2: Day 22/Day 50(N=1108,556)	91 percentages of subjects Interval 89.0 to 93.0	NA percentages of subjects Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	91 percentages of subjects Interval 88.0 to 93.0	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS immunogenicity set

Immunogenicity was measured in subjects (Previously vaccinated and Not previously vaccinated) as the geometric mean ratio (GMR). The ratio of postvaccination to prevaccination HI GMTs, three weeks after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c .For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c The CHMP criterion for GMR in adult population is \>2.5

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Geometric Mean Ratios (GMR) in Subjects After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years Age A/H1N1: TIV1c/QIVc [Day 22 (Day 50)/Day1]	11 Ratios Interval 10.0 to 13.0	12 Ratios Interval 10.0 to 13.0	NA Ratios Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Ratios (GMR) in Subjects After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years Age A/H3N2: TIV1c/QIVc [Day 22 (Day 50)/Day1]	3.65 Ratios Interval 3.4 to 3.91	3.97 Ratios Interval 3.59 to 4.38	NA Ratios Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Ratios (GMR) in Subjects After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years Age B1: TIV1c/QIVc [Day 22 (Day 50)/Day1]	6.15 Ratios Interval 5.72 to 6.61	6.24 Ratios Interval 5.64 to 6.91	NA Ratios Participants in the TIV2c Arm/Group were not vaccinated with the H1N1, H3N2 and B1 strains	—	—	—	—	—	—	—	—	—	—	—	—
Geometric Mean Ratios (GMR) in Subjects After One or Two Doses of Either QIVc, TIV1c or TIV2c in ≥4 to <18 Years Age B2: TIV2c/QIVc [Day 22 (Day 50)/Day1]	8.17 Ratios Interval 7.5 to 8.89	NA Ratios Participants in the TIV1c Arm/Group were not vaccinated with the B2 strain	8.45 Ratios Interval 7.5 to 9.53	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS population

Immunogenicity of QIVc to comparator TIV1c was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by HI assay, three weeks after last vaccination with one or two doses of either QIVc or TIV1c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV1c /GMT QIVc) for HI antibody did not exceed the superiority margin of 1

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
GMT in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c Against B2 Strain Day1(N=1108,563)	22 Titers Interval 20.0 to 24.0	21 Titers Interval 18.0 to 23.0	—	—	—	—	—	—	—	—	—	—	—	—	—
GMT in Subjects After Receiving One or Two Doses of Either QIVc, TIV1c Against B2 Strain Day 22/Day 50(N=1108,563)	176 Titers Interval 164.0 to 189.0	45 Titers Interval 41.0 to 49.0	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS population

Immunogenicity of QIVc to comparator TIV1c in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, against influenza strain B2, three weeks after last vaccination with QIVc or TIV1c. Superiority criterion was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV1c - % seroconversion QIVc) for HI antibody does not exceed the margin of 0 points

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving Seroconversion Against B2 Strain After One or Two Doses of Either QIVc or TIV1c	73 percentages of subjects Interval 70.0 to 76.0	26 percentages of subjects Interval 23.0 to 30.0	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1, Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS population

Immunogenicity of QIVc to comparator TIV2c was assessed in terms of GMT in subjects (Previously vaccinated and Not previously vaccinated) measured by HI assay, three weeks after last vaccination with one or two doses of either QIVc or TIV2c. Superiority was established if the upper bound of the two-sided 95% CI for the ratio of GMTs (GMT TIV2c /GMT QIVc) for HI antibody does not exceed the superiority margin of 1

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
GMT in Subjects After Receiving One or Two Doses of Either QIVc,TIV2c Against B1 Strain Day1(N=1112,557)	25 Titers Interval 23.0 to 27.0	24 Titers Interval 22.0 to 27.0	—	—	—	—	—	—	—	—	—	—	—	—	—
GMT in Subjects After Receiving One or Two Doses of Either QIVc,TIV2c Against B1 Strain Day 22/Day 50(N=1112,557)	154 Titers Interval 145.0 to 163.0	59 Titers Interval 54.0 to 64.0	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Three weeks post vaccination (Day 22 for previously vaccinated and Day 50 for Not previously vaccinated subjects)

Population: Analysis was done on FAS population

Immunogenicity of QIVc to comparator TIV2c in terms of number (%) of subjects (Previously vaccinated and Not previously vaccinated) showing seroconversion or significant increase in HI antibody titers, against influenza strain B1, three weeks after last vaccination with QIVc or TIV2c. Superiority was established if the upper bound of the two-sided 95% CI for the difference between seroconversion rates (% seroconversion TIV2c - % seroconversion QIVc) for HI antibody does not exceed the margin of 0 points

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Percentages of Subjects Achieving Seroconversion After One or Two Doses of Either QIVc or TIV2c	67 percentages of subjects Interval 64.0 to 70.0	33 percentages of subjects Interval 29.0 to 37.0	—	—	—	—	—	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to 7 after last vaccination

Population: Analysis was done on solicited safety data set i.e. all subjects in the exposed set with solicited adverse event data

Safety was assessed in terms of number of subjects (Previously vaccinated and Not previously vaccinated) reporting solicited local and systemic reactions, day 1 to 7 after last vaccination with one or two doses of either QIVc, TIV1c or TIV2c.For A/H1N1, A/H3N2 and B1 strain, the comparison was between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison is between QIVc and TIV2c.

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=182 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=91 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=93 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) n=98 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) n=39 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) n=47 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) n=372 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) n=185 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) n=186 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) n=205 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) n=112 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) n=116 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) n=579 Participants Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) n=294 Participants Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) n=282 Participants Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Erythema	32 Subjects	21 Subjects	16 Subjects	17 Subjects	3 Subjects	7 Subjects	83 Subjects	43 Subjects	38 Subjects	29 Subjects	17 Subjects	19 Subjects	110 Subjects	51 Subjects	43 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Pain	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	201 Subjects	105 Subjects	107 Subjects	95 Subjects	61 Subjects	62 Subjects	334 Subjects	150 Subjects	142 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Change of eating habits	19 Subjects	6 Subjects	6 Subjects	9 Subjects	3 Subjects	1 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Vomiting	8 Subjects	2 Subjects	2 Subjects	3 Subjects	0 Subjects	0 Subjects	12 Subjects	6 Subjects	6 Subjects	7 Subjects	2 Subjects	1 Subjects	10 Subjects	4 Subjects	5 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Diarrhea	8 Subjects	2 Subjects	2 Subjects	3 Subjects	1 Subjects	2 Subjects	13 Subjects	11 Subjects	9 Subjects	4 Subjects	4 Subjects	1 Subjects	22 Subjects	11 Subjects	9 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Loss of appetite	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	33 Subjects	10 Subjects	15 Subjects	6 Subjects	9 Subjects	8 Subjects	51 Subjects	25 Subjects	25 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Body temperature(>=38C)	7 Subjects	4 Subjects	3 Subjects	4 Subjects	1 Subjects	0 Subjects	16 Subjects	5 Subjects	4 Subjects	6 Subjects	2 Subjects	2 Subjects	7 Subjects	8 Subjects	4 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Analgesics and antipyretics-Preventive	13 Subjects	1 Subjects	1 Subjects	2 Subjects	1 Subjects	0 Subjects	14 Subjects	6 Subjects	8 Subjects	7 Subjects	4 Subjects	4 Subjects	15 Subjects	6 Subjects	8 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Analgesics and antipyretics-Treatment	12 Subjects	4 Subjects	3 Subjects	2 Subjects	2 Subjects	1 Subjects	27 Subjects	13 Subjects	10 Subjects	15 Subjects	4 Subjects	10 Subjects	24 Subjects	20 Subjects	14 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Tenderness	83 Subjects	41 Subjects	40 Subjects	49 Subjects	15 Subjects	15 Subjects	1 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Any local	103 Subjects	51 Subjects	47 Subjects	52 Subjects	17 Subjects	17 Subjects	237 Subjects	124 Subjects	116 Subjects	102 Subjects	64 Subjects	66 Subjects	377 Subjects	175 Subjects	156 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Nausea	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	29 Subjects	9 Subjects	10 Subjects	7 Subjects	6 Subjects	4 Subjects	55 Subjects	24 Subjects	21 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Ecchymosis	16 Subjects	10 Subjects	7 Subjects	6 Subjects	3 Subjects	2 Subjects	35 Subjects	17 Subjects	14 Subjects	9 Subjects	9 Subjects	7 Subjects	24 Subjects	16 Subjects	13 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Induration	24 Subjects	18 Subjects	12 Subjects	11 Subjects	2 Subjects	4 Subjects	59 Subjects	35 Subjects	24 Subjects	25 Subjects	18 Subjects	12 Subjects	88 Subjects	43 Subjects	36 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Any systemic	51 Subjects	18 Subjects	17 Subjects	30 Subjects	9 Subjects	9 Subjects	117 Subjects	67 Subjects	65 Subjects	46 Subjects	30 Subjects	27 Subjects	232 Subjects	121 Subjects	94 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Sleepiness	34 Subjects	11 Subjects	9 Subjects	13 Subjects	3 Subjects	5 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Chills	10 Subjects	2 Subjects	1 Subjects	4 Subjects	2 Subjects	1 Subjects	16 Subjects	6 Subjects	8 Subjects	2 Subjects	3 Subjects	0 Subjects	43 Subjects	17 Subjects	10 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Irritability	29 Subjects	9 Subjects	9 Subjects	15 Subjects	6 Subjects	6 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Myalgia	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	43 Subjects	26 Subjects	19 Subjects	18 Subjects	11 Subjects	11 Subjects	94 Subjects	50 Subjects	41 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Arthralgia	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	13 Subjects	10 Subjects	7 Subjects	6 Subjects	5 Subjects	4 Subjects	36 Subjects	19 Subjects	22 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Headache	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	52 Subjects	24 Subjects	23 Subjects	9 Subjects	8 Subjects	7 Subjects	127 Subjects	68 Subjects	50 Subjects
Number of Subjects Reporting Solicited Adverse Events (AEs) After One or Two Doses of Either QIVc, TIV1c or TIV2c by Age Sub-strata Fatigue	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	0 Subjects	47 Subjects	26 Subjects	33 Subjects	18 Subjects	12 Subjects	10 Subjects	104 Subjects	46 Subjects	44 Subjects

SECONDARY outcome

Timeframe: Day 1 to 210 post vaccination

Population: Analysis was done on unsolicited safety data set i.e. all subjects in the exposed set with unsolicited adverse event data

Safety was assessed in terms of number of subjects (Previously vaccinated and Not previously vaccinated) reporting unsolicited AEs (day 1 to 22 for Previously vaccinated and day 1 to day 50 for Not previously vaccinated subjects), serious adverse events (SAEs), medically attended AEs, AEs leading to withdrawal from the study, new onset of chronic diseases (NOCDs), and concomitant medications (day 1 to day 181 for Previously vaccinated and day 1 to day 210 for Not previously vaccinated subjects) after receiving one or two doses of either QIVc, TIV1c or TIV2c. For A/H1N1, A/H3N2 and B1 strain, the comparison is between QIVc and TIV1c and for B2 i.e. alternate B strain, the comparison was between QIVc and TIV2c.

Outcome measures

Outcome measures
Measure	QIVc (≥4 to <18 Years) n=1159 Participants Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥4 to <18 Years) n=593 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥4 to <18 Years) n=581 Participants Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥4 to <6 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2,B1) recommended for 2013-2014 season	TIV2c _First Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c_Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c _Second Vaccine (≥6 to <9 Years) Subjects received one or two doses of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014	QIVc (≥9 to <18 Years) Subjects received one dose of cell derived quadrivalent influenza vaccine (QIVc) recommended for 2013-2014 season	TIV1c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV1c (H1N1, H3N2, B1) recommended for 2013-2014 season	TIV2c (≥9 to <18 Years) Subjects received one dose of cell derived trivalent influenza vaccine TIV2c that contains an alternate B strain compared to what is recommended for 2013-2014
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group Possibly/probably related AE	56 Subjects	34 Subjects	31 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group SAE	6 Subjects	7 Subjects	2 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group Possibly/probably related SAE	0 Subjects	0 Subjects	0 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group AE leading to study withdrawal	0 Subjects	1 Subjects	0 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group Any AE	279 Subjects	139 Subjects	152 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group Medically attended AE	310 Subjects	156 Subjects	153 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group NOCD	20 Subjects	11 Subjects	11 Subjects	—	—	—	—	—	—	—	—	—	—	—	—
Number of Subjects Reporting Unsolicited AEs After One or Two Doses of Either QIVc, TIV1c or TIV2c by Overall Age Group Death	0 Subjects	0 Subjects	0 Subjects	—	—	—	—	—	—	—	—	—	—	—	—

Adverse Events

QIVc

Serious events: 6 serious events

Other events: 840 other events

Deaths: 0 deaths

TIV1c

Serious events: 7 serious events

Other events: 417 other events

Deaths: 0 deaths

TIV2c

Serious events: 2 serious events

Other events: 392 other events

Deaths: 0 deaths

Total

Serious events: 15 serious events

Other events: 1649 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Posting Director

Novartis Vaccines and Diagnostics

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER