Trial Outcomes & Findings for Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of QIVc in Subjects ≥2 to <18 Years of Age (NCT NCT03165617)

Last Updated: 2020-10-22

Results Overview

The primary efficacy endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of either RT-PCR- or culture-confirmed influenza (time-to-event analyses) due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season. Dataset Used: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination. The success criterion used for this primary objective was as follows: The efficacy of the QIVc was demonstrated if the lower limit (LL) of the 2-sided 95% confidence interval (CI) for VE was above 20%.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

4514 participants

Primary outcome timeframe

Day 14 to Day 180 or until the end of the influenza season, whichever is longer

Results posted on

2020-10-22

Participant Flow

Subjects were enrolled over 3 seasons, starting in SH 2017, followed by NH 2017-2018 and NH 2018-2019. Recruitment was conducted in 8 countries over these 3 seasons: Australia, Philippines and Thailand (Season 1); Estonia and Finland i(Season 2); and Estonia, Finland, Lithuania, Poland and Spain (Season 3)

Participant milestones

Participant milestones
Measure	QIVc (≥2 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Overall Study STARTED	2258	2256
Overall Study COMPLETED	2249	2247
Overall Study NOT COMPLETED	9	9

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Clinical Study to Evaluate the Efficacy, Safety and Immunogenicity of QIVc in Subjects ≥2 to <18 Years of Age

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	QIVc (≥2 Years to <18 Years of Age) n=2258 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2256 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	Total n=4514 Participants Total of all reporting groups
Age, Continuous	8.7 years STANDARD_DEVIATION 4.00 • n=5 Participants	8.9 years STANDARD_DEVIATION 4.11 • n=7 Participants	8.8 years STANDARD_DEVIATION 4.06 • n=5 Participants
Sex: Female, Male Female	1106 Participants n=5 Participants	1082 Participants n=7 Participants	2188 Participants n=5 Participants
Sex: Female, Male Male	1152 Participants n=5 Participants	1174 Participants n=7 Participants	2326 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	11 Participants n=5 Participants	11 Participants n=7 Participants	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	2245 Participants n=5 Participants	2245 Participants n=7 Participants	4490 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1106 Participants n=5 Participants	1100 Participants n=7 Participants	2206 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	1140 Participants n=5 Participants	1139 Participants n=7 Participants	2279 Participants n=5 Participants
Race (NIH/OMB) More than one race	NA Participants n=5 Participants	NA Participants n=7 Participants	NA Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	11 Participants n=5 Participants	15 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment Philippines	902 Participants n=5 Participants	898 Participants n=7 Participants	1800 Participants n=5 Participants
Region of Enrollment Finland	168 Participants n=5 Participants	158 Participants n=7 Participants	326 Participants n=5 Participants
Region of Enrollment Poland	147 Participants n=5 Participants	151 Participants n=7 Participants	298 Participants n=5 Participants
Region of Enrollment Australia	96 Participants n=5 Participants	99 Participants n=7 Participants	195 Participants n=5 Participants
Region of Enrollment Thailand	201 Participants n=5 Participants	199 Participants n=7 Participants	400 Participants n=5 Participants
Region of Enrollment Lithuania	142 Participants n=5 Participants	150 Participants n=7 Participants	292 Participants n=5 Participants
Region of Enrollment Estonia	599 Participants n=5 Participants	599 Participants n=7 Participants	1198 Participants n=5 Participants
Region of Enrollment Spain	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer

Population: FAS Efficacy - All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2257 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2252 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Primary Efficacy: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥2 to <18 Years	175 Number of cases	364 Number of cases	—	—	—	—	—	—

PRIMARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer

Population: FAS Efficacy - All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

The co-primary efficacy endpoint: was defined as the time from the last study vaccination to the onset of the first occurrence of either RT-PCR- or culture-confirmed influenza (time-to-event analyses) due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season.Absolute vaccine efficacy of QIVc by first occurrence RT-PCR or culture confirmed influenza, due to any influenza Type A and B strain in subjects ≥3 years to \<18 years of age

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2208 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2201 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Co-Primary: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza (Time-to-event Analyses) Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine in Subjects ≥3 to <18 Years	171 Number of cases	351 Number of cases	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

Population: FAS Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

The endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of either RT-PCR- or culture-confirmed influenza due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to \<18 years, 2 to \<9 years, 4 to \<18 years, and 9 to \<18 years. Dataset used: FAS Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2257 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2252 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=1146 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=1142 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) n=2045 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) n=2032 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) n=1111 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) n=1110 Participants Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Efficacy #1: First Occurrence of Either RT-PCR- or Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine	175 Number of cases	364 Number of cases	123 Number of cases	234 Number of cases	154 Number of cases	310 Number of cases	52 Number of cases	130 Number of cases

SECONDARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

Population: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

The endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of RT-PCR-confirmed influenza due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to \<18 years, 2 to \<9 years, 4 to \<18 years, and 9 to \<18 years Dataset used: FAS Efficacy - All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2257 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2252 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=1146 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=1142 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) n=2045 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) n=2032 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) n=1111 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) n=1110 Participants Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Efficacy #2: First Occurrence of RT-PCR-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine	175 Number of cases	364 Number of cases	123 Number of cases	234 Number of cases	154 Number of cases	310 Number of cases	52 Number of cases	130 Number of cases

SECONDARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

Population: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

The secondary endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of culture-confirmed influenza due to any influenza Type A or B strain regardless of antigenic match to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to \<18 years, 2 to \<9 years, 4 to \<18 years, and 9 to \<18 years. Dataset used: FAS Efficacy

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2257 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2252 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=1146 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=1142 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) n=2045 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) n=2032 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) n=1111 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) n=1110 Participants Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Efficacy #3: First Occurrence of Culture-confirmed Influenza Due to Any Influenza Type A or B Strain Regardless of Antigenic Match to the Strains Selected for the Seasonal Vaccine	115 Number of cases	279 Number of cases	79 Number of cases	190 Number of cases	101 Number of cases	237 Number of cases	36 Number of cases	89 Number of cases

SECONDARY outcome

Timeframe: Day 14 to Day 180 or until the end of the influenza season, whichever is longer.

Population: FAS-Efficacy = All subjects in the All Enrolled Set who received at least one dose of study vaccine and were evaluated for efficacy from 14 days after the last vaccination.

The endpoint was defined as the time from the last study vaccination to the onset of the first occurrence of culture-confirmed influenza due to influenza Type A or B strain antigenically matched to the strains selected for the seasonal vaccine, that occurred more than 14 days after the last vaccination until the end of the influenza season in subjects 2 to \<18 years, 2 to \<9 years, 4 to \<18 years, and 9 to \<18 years.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2257 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2252 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=1146 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=1142 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) n=2045 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) n=2032 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) n=1111 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) n=1110 Participants Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Efficacy #4: First Occurrence of Culture-confirmed Influenza Due to Influenza Type A or B Strain Antigenically Matched to the Strains Selected for the Seasonal Vaccine	90 Number of cases	236 Number of cases	64 Number of cases	164 Number of cases	81 Number of cases	200 Number of cases	26 Number of cases	72 Number of cases

SECONDARY outcome

Timeframe: Day 1 (all subjects), Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects receiving 2 doses)

Population: FAS Immunogenicity - All Subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline at after the last vaccination

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=210 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=212 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=154 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=145 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) A/H3N2 Day 1 HI GMT	97.02 Geometric mean titers (GMTs) Interval 86.51 to 108.81	94.40 Geometric mean titers (GMTs) Interval 84.19 to 105.84	20.85 Geometric mean titers (GMTs) Interval 15.99 to 27.2	20.74 Geometric mean titers (GMTs) Interval 16.02 to 26.85	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) A/H1N1 Day 1 HI GMT	50.83 Geometric mean titers (GMTs) Interval 41.89 to 61.66	47.51 Geometric mean titers (GMTs) Interval 39.15 to 57.64	36.62 Geometric mean titers (GMTs) Interval 22.61 to 59.31	31.76 Geometric mean titers (GMTs) Interval 19.88 to 50.74	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) A/H1N1 Day 22/50 HI GMT	283.45 Geometric mean titers (GMTs) Interval 249.22 to 322.38	49.20 Geometric mean titers (GMTs) Interval 43.24 to 55.98	380.70 Geometric mean titers (GMTs) Interval 283.12 to 511.91	48.22 Geometric mean titers (GMTs) Interval 36.14 to 64.32	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) A/H3N2 Day 22/50 HI GMT	168.73 Geometric mean titers (GMTs) Interval 150.87 to 188.7	96.27 Geometric mean titers (GMTs) Interval 86.05 to 107.7	67.64 Geometric mean titers (GMTs) Interval 57.03 to 80.24	16.73 Geometric mean titers (GMTs) Interval 14.17 to 19.77	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) B/Victoria Day 1 HI GMT	11.67 Geometric mean titers (GMTs) Interval 9.97 to 13.67	11.73 Geometric mean titers (GMTs) Interval 10.02 to 13.73	9.54 Geometric mean titers (GMTs) Interval 7.25 to 12.54	9.41 Geometric mean titers (GMTs) Interval 7.22 to 12.28	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) B/Victoria Day 22/50 HI GMT	45.25 Geometric mean titers (GMTs) Interval 39.73 to 51.54	11.94 Geometric mean titers (GMTs) Interval 10.48 to 13.6	66.82 Geometric mean titers (GMTs) Interval 51.29 to 87.04	11.94 Geometric mean titers (GMTs) Interval 9.23 to 15.44	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) B/Yamagata Day 1 HI GMT	10.87 Geometric mean titers (GMTs) Interval 9.46 to 12.5	12.17 Geometric mean titers (GMTs) Interval 10.59 to 13.99	23.98 Geometric mean titers (GMTs) Interval 16.74 to 34.36	27.33 Geometric mean titers (GMTs) Interval 19.27 to 38.76	—	—	—	—
Secondary Immunogenicity: Geometric Mean Titers for 4 Influenza Strains (HI Assay) B/Yamagata Day 22/50 HI GMT	52.81 Geometric mean titers (GMTs) Interval 45.77 to 60.94	12.34 Geometric mean titers (GMTs) Interval 10.68 to 14.24	108.49 Geometric mean titers (GMTs) Interval 85.16 to 138.22	21.68 Geometric mean titers (GMTs) Interval 17.11 to 27.46	—	—	—	—

SECONDARY outcome

Timeframe: Day 22 (all previously vaccinated subjects) or Day 29 and Day 50 (all not previously vaccinated subjects)

Population: FAS Immunogenicity: all subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.

Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to \<9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay. Seroconversion was defined as: either a prevaccination HI titer \<1:10 and a postvaccination HI titer ≥1:40 or a prevaccination HI titer ≥1:10 and a ≥4 fold increase in postvaccination HI titer) Dataset used: FAS Immunogenicity = All subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=210 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=212 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=154 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=145 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay) A/H1N1	59.5 Percentage of participants Interval 52.55 to 66.22	1.9 Percentage of participants Interval 0.52 to 4.8	74.0 Percentage of participants Interval 66.35 to 80.75	6.2 Percentage of participants Interval 2.88 to 11.46	—	—	—	—
ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay) A/H3N2	19.0 Percentage of participants Interval 13.97 to 25.02	1.9 Percentage of participants Interval 0.52 to 4.8	51.9 Percentage of participants Interval 43.76 to 60.06	1.4 Percentage of participants Interval 0.17 to 4.89	—	—	—	—
ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay) B/Victoria	40.0 Percentage of participants Interval 33.32 to 46.97	2.9 Percentage of participants Interval 1.06 to 6.11	58.4 Percentage of participants Interval 50.23 to 66.32	3.4 Percentage of participants Interval 1.13 to 7.86	—	—	—	—
ISecondary Immunogenicity: Percentage of Subjects Achieving Seroconversion for 4 Influenza Strains (HI Assay) B/Yamagata	49.5 Percentage of participants Interval 42.57 to 56.49	4.8 Percentage of participants Interval 2.31 to 8.58	58.4 Percentage of participants Interval 50.23 to 66.32	1.4 Percentage of participants Interval 0.17 to 4.89	—	—	—	—

SECONDARY outcome

Timeframe: Day 22/Day 1 (all previously vaccinated subjects) or Day 29/Day 1 and Day 50/Day 1 (all not previously vaccinated subjects receiving 2 doses)

Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to \<9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay. Geometric mean ratios (GMRs) measure the ratio in immunogenicity titers within subject\\ Dataset used: FAS Immunogenicity = All subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=210 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=212 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=154 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=145 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay) A/H1N1	5.76 Geometric mean ratio (GMR) Interval 5.06 to 6.55	1.00 Geometric mean ratio (GMR) Interval 0.88 to 1.14	9.73 Geometric mean ratio (GMR) Interval 7.24 to 13.09	1.23 Geometric mean ratio (GMR) Interval 0.92 to 1.64	—	—	—	—
Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay) A/H3N2	1.74 Geometric mean ratio (GMR) Interval 1.56 to 1.95	0.99 Geometric mean ratio (GMR) Interval 0.89 to 1.11	4.14 Geometric mean ratio (GMR) Interval 3.49 to 4.91	1.02 Geometric mean ratio (GMR) Interval 0.87 to 1.21	—	—	—	—
Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay) B/Victoria	3.79 Geometric mean ratio (GMR) Interval 3.33 to 4.32	1.00 Geometric mean ratio (GMR) Interval 0.88 to 1.14	7.01 Geometric mean ratio (GMR) Interval 5.38 to 9.14	1.25 Geometric mean ratio (GMR) Interval 0.97 to 1.62	—	—	—	—
Secondary Immunogenicity: Geometric Mean Ratio for 4 Influenza Strains (HI Assay) B/Yamagata	4.63 Geometric mean ratio (GMR) Interval 4.01 to 5.34	1.08 Geometric mean ratio (GMR) Interval 0.94 to 1.25	5.27 Geometric mean ratio (GMR) Interval 4.14 to 6.72	1.05 Geometric mean ratio (GMR) Interval 0.83 to 1.33	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 (all subjects), Day 22 (all "previously vaccinated" subjects receiving a single vaccine dose) or Days 29 and 50 (all "not previously vaccinated"subjects receiving 2 doses)

Population: Dataset used: FAS Immunogenicity = all subjects in the All Enrolled Set who received at least one dose of study vaccine and provided evaluable serum samples at both baseline and after the last vaccination.

Immunogenicity was characterized by HI assay 3 weeks after the last vaccination in a subset of subjects 2 to \<9 years of age enrolled in Season 2 (n=432) and Season 3 (n=319) who were immunized and had immunogenicity data at the assessed timepoints (FAS Immunogenicity). Immunogenicity was assessed at baseline (Day 1; all subjects in immunogenicity subset), at Day 22 (all "previously vaccinated" subjects receiving a single dose of the study vaccine), and at Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains using the HI assay. The measures for assessing immunogenicity as determined by HI were as follows: Percentage of subjects with an HI titer ≥1:40 on Day 22 (all "previously vaccinated" subjects receiving a single vaccine dose) or Days 29 and 50 (all "not previously vaccinated" subjects receiving 2 doses) for all 4 influenza strains

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=210 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=212 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) n=154 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) n=145 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay) A/H1N1	88.6 Percentage of participants Interval 83.47 to 92.54	58.6 Percentage of participants Interval 51.59 to 65.31	94.8 Percentage of participants Interval 90.02 to 97.73	55.2 Percentage of participants Interval 46.7 to 63.43	—	—	—	—
Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay) A/H3N2	90.0 Percentage of participants Interval 85.12 to 93.7	92.4 Percentage of participants Interval 87.92 to 95.58	74.0 Percentage of participants Interval 66.35 to 80.75	24.8 Percentage of participants Interval 18.03 to 32.68	—	—	—	—
Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay) B/Victoria	54.3 Percentage of participants Interval 47.29 to 61.16	24.30 Percentage of participants Interval 18.65 to 30.66	68.8 Percentage of participants Interval 60.88 to 76.04	13.1 Percentage of participants Interval 8.08 to 19.7	—	—	—	—
Secondary Immunogenicity: Percentage of Subjects With HI Titer ≥1:40 for All 4 Influenza Strains (HI Assay) B/Yamagata	63.8 Percentage of participants Interval 56.91 to 70.31	21.4 Percentage of participants Interval 16.08 to 27.6	79.2 Percentage of participants Interval 71.95 to 85.33	46.2 Percentage of participants Interval 37.9 to 54.67	—	—	—	—

SECONDARY outcome

Timeframe: days after vaccination on Day 1 (for "previously vaccinated" subjects) or for 7 days after vaccination on Day 1 and Day 29 (for "not previously vaccinated" subjects)

Population: Dataset used: Solicited Safety Set = All subjects in the Exposed Set who had gone through any assessment of local and systemic site reaction and/or assessment of any use of analgesics/antipyretics. Note: Other solicited adverse events refer to use of analgesics / antipyretics for prophylaxis or treatment.

The measures for assessing safety and tolerability were as follows: Percentage of subjects with solicited local and systemic adverse events (AEs) for 7 days after vaccination on Day 1 (for "previously vaccinated" subjects) or for 7 days after vaccination on Day 1 and Day 29 (for "not previously vaccinated" subjects) in the QIVc group and the non-influenza comparator vaccine group. Dataset used: Solicited Safety Set

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2255 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2254 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination Solicited AEs	51.4 Percentage of participants	48.6 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination Solicited Local AEs	36.8 Percentage of participants	33.6 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination Solicited Systemic AEs	31.4 Percentage of participants	30.5 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Solicited Local and Systemic Adverse Events for 7 Days After Vaccination Other	8.6 Percentage of participants	7.3 Percentage of participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 22 (for previously vaccinated subjects) or Day 1 to Day 50 (for not previously vaccinated subjects)

Population: Dataset used: unsolicited Safety Set defined as all subjects in the Exposed Set who had gone through any AE assessments, ie, a subject did not have to have any AEs to be included in this population

The measures for assessing safety and tolerability were as follows: Percentage of subjects with unsolicited AEs assessed from Day 1 to Day 22 (for "previously vaccinated" subjects) or from Day 1 to Day 50 (for "not previously vaccinated" subjects) in the QIVc group and the non-influenza comparator vaccine group. Dataset used: Unsolicited Safety Set (Unsolicited Adverse Events)

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2258 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2255 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination Any AE	28.0 Percentage of participants	27.9 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination Any AE (Mild)	24.4 Percentage of participants	24.6 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination Any AE (Moderate)	4.8 Percentage of participants	4.5 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination Any AE (Severe)	0.5 Percentage of participants	0.5 Percentage of participants	—	—	—	—	—	—
Safety: Percentage of Subjects With Unsolicited AEs for 21 Days After Vaccination Related AE	4.3 Percentage of participants	3.9 Percentage of participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Day 1 to Day 181 (for previously vaccinated subjects) or to Day 209 (for not previously vaccinated subjects)

Population: Dataset used: overall safety set defined as all subjects in the Solicited Safety Set and/or Unsolicited Safety Set. Subjects providing only 30 minutes postvaccination safety data were also reported separately in a 30-minute postvaccination safety analysis.

The measures for assessing safety and tolerability were as follows: Percentage of subjects with SAEs, AEs leading to withdrawal from vaccination and/or the study, Medically-Attended AEs (MAAEs) within 30 days after the first occurrence of an ILI, and New Onset of Chronic Diseases (NOCDs) reported during the subject's entire participation in the study (ie, from Day 1 to Day 181 \[for "previously vaccinated" subjects\] or from Day 1 to Day 209 \[for "not previously vaccinated" subjects\]), or until the end of influenza season, whichever was longer, and all medications associated with these events. Dataset used: Overall Safety Set

Outcome measures

Outcome measures
Measure	QIVc (≥2 Years to <18 Years of Age) n=2258 Participants Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2255 Participants Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥2 Years to <9 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥2 Years to <9 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥4 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥4 Years to <18 Years of Age) Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use	QIVc (≥9 Years to <18 Years of Age) Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Comparator (≥9 Years to <18 Years of Age) Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer SAE	1.1 Percentage of participants	1.3 Percentage of participants	—	—	—	—	—	—
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer Related SAE	0 Percentage of participants	0 Percentage of participants	—	—	—	—	—	—
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer AE leading to study withdrawal	0 Percentage of participants	0 Percentage of participants	—	—	—	—	—	—
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer MAAE	27.2 Percentage of participants	30.1 Percentage of participants	—	—	—	—	—	—
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer NOCD	0.4 Percentage of participants	0.5 Percentage of participants	—	—	—	—	—	—
Safety: Subjects With SAEs, AEs Leading to Withdrawal From Vaccination and/or the Study,(MAAEs) Within 30 Days of a 1st Occurrence, Post-ILI, and NOCDs Reported During Entire Study Participation or End of Flue Season, Whichever Was Longer Death	0 Percentage of participants	0.04 Percentage of participants	—	—	—	—	—	—

Adverse Events

QIVc (≥2 Years to <18 Years of Age)

Serious events: 25 serious events

Other events: 871 other events

Deaths: 0 deaths

Non-Influenza Comparator Vaccine

Serious events: 30 serious events

Other events: 963 other events

Deaths: 1 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	QIVc (≥2 Years to <18 Years of Age) n=2258 participants at risk Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2255 participants at risk Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
General disorders Influenza like illness	35.0% 791/2258 • Number of events 791 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	39.6% 894/2255 • Number of events 894 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Nasopharyngitis	4.9% 111/2258 • Number of events 111 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	6.0% 135/2255 • Number of events 135 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Upper respiratory tract infection	13.2% 298/2258 • Number of events 298 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	12.0% 270/2255 • Number of events 270 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported

Additional Information

Seqirus Clinical Trial Manager

Seqirus

Phone: 1-855-358-8966

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	QIVc (≥2 Years to <18 Years of Age) n=2258 participants at risk Cell-derived Seasonal Quadrivalent Influenza Vaccine QIVc: Cell-derived Quadrivalent Influenza Vaccine for intramuscular use containing each of the 2 influenza type A strains and each of the 2 influenza type B strains	Non-Influenza Comparator Vaccine n=2255 participants at risk Non-Influenza Comparator Vaccine Non-influenza Comparator Vaccine: Non-influenza comparator vaccine for intramuscular use
Injury, poisoning and procedural complications Clavicle fracture	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Injury, poisoning and procedural complications Hand fracture	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Injury, poisoning and procedural complications Contusion	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Injury, poisoning and procedural complications Ligament rupture	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Injury, poisoning and procedural complications Multiple fractures	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Nervous system disorders Neuropathy, peripheral	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Nervous system disorders Speech disorder developmental	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Nervous system disorders Brain Edema	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Nervous system disorders Loss of consciousness	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Nervous system disorders Status Migrainosus	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
General disorders Unevaluable event	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Psychiatric disorders Anorexia nervosa	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Gastrointestinal disorders Gastritis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Gastrointestinal disorders Irritable Bowel Syndrome	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Gastrointestinal disorders Nausea	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Skin and subcutaneous tissue disorders Drug eruption	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Skin and subcutaneous tissue disorders Urticaria	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Metabolism and nutrition disorders Diabetic Ketoacidosis	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Metabolism and nutrition disorders Type I Diabetes Mellitus	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Pharyngitis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Tonsillitis bacterial	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Chronic Tonsillitis	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Pneumonia	0.22% 5/2258 • Number of events 5 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.13% 3/2255 • Number of events 3 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Dengue fever	0.09% 2/2258 • Number of events 2 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.09% 2/2255 • Number of events 2 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Pneumonia mycoplasma	0.09% 2/2258 • Number of events 2 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Appendicitis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.09% 2/2255 • Number of events 2 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Appendicitis perforated	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Bronchitis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Campylobacter gastroenteritis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Dengue hemorrhagic fever	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Enterococcal Gastroenteritis	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Gastrointestinal viral infection	0.04% 1/2258 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.00% 0/2255 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Gastroenteritis	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Gastroenteritis rotavirus	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Impetigo	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Otitis media chronic	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Otitis media	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.09% 2/2255 • Number of events 2 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Pneumonia bacterial	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Urinary tract infection	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.13% 3/2255 • Number of events 3 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Infections and infestations Viral infection	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported
Injury, poisoning and procedural complications Skull fracture	0.00% 0/2258 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported	0.04% 1/2255 • Number of events 1 • Day 1 through end of study Adverse event reporting additional description: Nonserious Unsolicited AEs and SAEs are reported