QHD04: Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03698279
• Collaborator: (none)
• Enrollment: 665
• Locations: 16
• Arms: 6
• Actual Duration (Months): 12.2
• Patients Per Site: 41.6
• Patients Per Site Per Month: 3.4

Study Details

Study Description

Brief Summary

The objectives of this study were:

• To describe the safety of each dosage of high-dose quadrivalent influenza vaccine (QIV-HD) used in the study during the 28 days following each vaccination, and serious adverse events (including adverse events of special interest throughout the study).

• To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD) by hemagglutination inhibition (HAI) measurement method.

• To describe the antibody response induced by each dosage of QIV-HD used in the study compared with unadjuvanted QIV-SD by virus seroneutralization (SN) measurement method.

• To describe the antibody response induced by the highest acceptable dosage of QIV-HD compared with adjuvanted trivalent influenza vaccine (TIV) by HAI and virus SN measurement methods.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated); Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated); Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated); Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated); Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated)	Phase 2

Detailed Description

Study duration per participant was approximately 180 days for participants who received one dose of vaccine and 208 days for participants who received two doses of vaccine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 665 participants
• Allocation: Randomized
• Intervention Model: Sequential Assignment
• Intervention Model Description: The study was divided into 13 groups and enrolled participants in 4 stages. The study used a stepwise age de-escalation and dose ascension design for children 6 months to less than (<) 5 years of age.The study was divided into 13 groups and enrolled participants in 4 stages. The study used a stepwise age de-escalation and dose ascension design for children 6 months to less than (<) 5 years of age.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Modified double-blind: the participant's parent / legally acceptable representative, the Investigator, and other study personnel remained unaware of the treatment assignments throughout the trial. An unblinded vaccine administrator administered the appropriate vaccine but was not involved in safety data collection.
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of Different Dosages of High-Dose Quadrivalent Influenza Vaccine in Children 6 Months to 17 Years of Age
• Actual Study Start Date: Oct 9, 2018
• Actual Primary Completion Date: Oct 16, 2019
• Actual Study Completion Date: Oct 16, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: QIV-HD 30 μg (US: 6 months to 17 years) Participants from United States (US) (aged 6 months to 17 years) received single injection of 30 microgram (μg) QIV-HD, intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 30 μg (split-virion, inactivated); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM
Experimental: Group 2: QIV-HD 45 μg (US: 6 months to 17 years) Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 45 μg, (split-virion, inactivated); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM
Experimental: Group 3: QIV-HD, 60 μg (US: 6 months to 17 years) Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM
Active Comparator: Group 4: Pooled QIV-SD, 15 μg (US: 6 months to 17 years) Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: Fluarix Quadrivalent Influenza vaccine (Unadjuvanted QIV-SD) (Inactivated); Pharmaceutical form: Solution for injection Route of administration: IM
Experimental: Group 5: QIV-HD, 60 μg (Canada: 6 to <24 months) Participants from Canada (aged 6 to less than [<] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 60 µg (split-virion, inactivated); Pharmaceutical form: Suspension for injection in pre-filled syringe Route of administration: IM
Active Comparator: Group 6: Adjuvanted TIV (Canada: 6 to <24 months) Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Biological: FLUAD Pediatric (adjuvanted TIV) (Surface Antigen, Inactivated); Pharmaceutical form: Solution for injection Route of administration: IM

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination [Within 30 minutes after any vaccination]

   An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.

2. Number of Participants With Unsolicited Adverse Events After Any Vaccination [Within 28 days after any vaccination]

   An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions.

3. Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination [From Day 0 up to 6 months (i.e. 180 days) post last vaccination]

   An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis.

4. Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 28 post any vaccination]

   Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer <10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (>=)40(1/dilution) at Day 28, or HAI titer >=10(1/dilution) at Day 0 and >=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.

5. Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 28 post any vaccination]

   GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Data for this OM was planned to be collected and reported for dose level (QIV-HD 30 μg and QIV-HD 45 μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to the complex study design and analysis of the dose formulation and age groups in the study, QIV-SD group participants, who matched to participants in the QIV-HD 30 μg and QIV-HD 45 μg dose formulations groups (who were 9 through 17 years old and shared a matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.

6. Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 0 (pre-vaccination), Day 28 (post any vaccination)]

   GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-vaccination and pre-vaccination.

7. Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 28 post any vaccination]

   GMT was measured for each influenza strain using HAI assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.

8. Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 28 post any vaccination]

   GMT was measured for each influenza strain using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.

9. Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine [Day 0 (pre-vaccination), Day 28 (post any vaccination)]

   GMTRs of anti-influenza antibodies were measured using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage and B/Yamagata lineage. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.

10. Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds [Day 28 post any vaccination]

    Neutralizing Antibody titer was measured for each influenza strain with SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage at pre-defined thresholds of >=20, >=40 and >=80 (1/dilution).

11. Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer [Day 28 post any vaccination]

    Neutralizing Antibody titer was measured for each influenza strain with SN method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / pre-vaccination computed value.

12. Number of Participants With Solicited Injection Site Reactions [Within 7 days after any vaccination]

    A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions included tenderness/pain, erythema, swelling, induration and bruising.

13. Number of Participants With Solicited Systemic Reactions After Any Vaccination [Within 7 days after any vaccination]

    A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss and irritability. Fever was planned to be evaluated for the whole population where as, the other events (vomiting, crying abnormal, drowsiness, appetite lost, and irritability) were planned to be evaluated only in the participants aged 6 months to <36 months.

14. Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months [Within 7 days after any vaccination]

    A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included: headache, malaise, myalgia and shivering.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion criteria :

• Aged 6 months to 17 years on the day of inclusion.

• Assent form was signed and dated by the participant (7 to 17 years of age) and informed consent form was signed and dated by the parent(s) or guardian(s) and by an independent witness, if required by local regulations.

• Participant and parent/guardian were able to attend all scheduled visits and complied with all study procedures.

• For participants aged <24 months: Born at full term of pregnancy (greater than or equal to [>=] 37 weeks) and/or with a birth weight >=2.5 kilogram.

Exclusion criteria:

• Participant was pregnant, or lactating, or of childbearing potential and not using an effective method of contraception or abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche.

• Participation at the time of study enrollment (or in the 4 weeks preceding the first study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure.

• Receipt of any vaccine in the 30 days preceding the first study vaccination, or planned receipt of any vaccine before Visit 3 for participants receiving 1 dose of influenza vaccine or Visit 5 for participants receiving 2 doses of influenza vaccine.

• For previously influenza vaccinated participants: Previous vaccination against influenza in the preceding 6 months with either the study vaccine or another vaccine.

• For previously influenza unvaccinated participants: Any influenza vaccination (from birth to the day of inclusion) with either the study vaccine or another influenza vaccine.

• For previously influenza unvaccinated participants: Any previous laboratory confirmed influenza infection (from birth to the day of inclusion)

• Receipt of immune globulins, blood or blood-derived products in the past 3 months.

• Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy, such as anti-cancer chemotherapy or radiation therapy, within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances.

• Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on Investigator's judgement.

• Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

• Current alcohol abuse or drug addiction.

• Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with study conduct or completion.

• Moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination or febrile illness (temperature >=38.0°Celsius [>=100.4°Fahrenheit]). A prospective participant should not be included in the study until the condition had resolved or the febrile event had subsided.

• Identified as an immediate family member (i.e., spouse, natural or adopted child, grandchild, nephew, or niece) of the Investigator or employee with direct involvement in the proposed study.

• Personal history of Guillain-Barré syndrome.

• Any condition that in the opinion of the Investigator would pose a health risk to the participant if enrolled or could interfere with the evaluation of the vaccine

• Personal history of clinically significant development delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder.

• Known seropositivity for hepatitis B or hepatitis C.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number 8400004	San Diego	California	United States	92123-1881
2	Investigational Site Number 8400001	Miami	Florida	United States	33186
3	Investigational Site Number 8400002	Atlanta	Georgia	United States	30322
4	Investigational Site Number 8400013	El Dorado	Kansas	United States	67042
5	Investigational Site Number 8400015	Newton	Kansas	United States	67114
6	Investigational Site Number 8400009	Wichita	Kansas	United States	67207
7	Investigational Site Number 8400007	Metairie	Louisiana	United States	70006
8	Investigational Site Number 8400010	Las Vegas	Nevada	United States	89104
9	Investigational Site Number 8400011	Warwick	Rhode Island	United States	02886
10	Investigational Site Number 8400003	Salt Lake City	Utah	United States	84107
11	Investigational Site Number 8400012	Salt Lake City	Utah	United States	84109
12	Investigational Site Number 8400005	Salt Lake City	Utah	United States	84121
13	Investigational Site Number 8400014	West Jordan	Utah	United States	84088-8865
14	Investigational Site Number 1241003	Montreal		Canada	H3T 1C5
15	Investigational Site Number 1241002	Pierrefonds		Canada	H9H 4Y6
16	Investigational Site Number 1241001	Quebec		Canada	G1E 7G9

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study Documents (Full-Text)

• Study Protocol - Feb 25, 2019
• Statistical Analysis Plan - Jul 4, 2019

More Information

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03698279
• Other Study ID Numbers: QHD04; U1111-1189-3713; 2018-005026-39
• First Posted: Oct 5, 2018
• Last Update Posted: Apr 4, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	The study was conducted at 16 centers in United States (US) and Canada from 09 October 2018 to 16 October 2019.
Pre-assignment Detail	A total of 665 participants were enrolled in the study.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 microgram (μg) high-dose quadrivalent influenza vaccine (QIV-HD), intramuscularly (IM) at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted standard-dose quadrivalent influenza vaccine (QIV-SD), IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to less than [<] 24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted trivalent influenza vaccine (TIV), IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Period Title: Overall Study
STARTED	124	122	159	234	13	13
Safety Analysis Set Population (SafAS)	122	121	158	234	13	13
COMPLETED	119	120	152	228	13	13
NOT COMPLETED	5	2	7	6	0	0

Baseline Characteristics

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)	Total
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Total of all reporting groups
Overall Participants	124	122	159	234	13	13	665
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	5.8 (3.91)	6.1 (4.30)	5.2 (4.22)	5.1 (4.02)	0.8 (0.19)	1.0 (0.28)	5.3 (4.13)
Age, Customized (Count of Participants)
6 - < 24 months	0 0%	0 0%	0 0%	0 0%	13 100%	13 100%	26 3.9%
6 - < 36 months	29 23.4%	30 24.6%	54 34%	75 32.1%	0 0%	0 0%	188 28.3%
36 months - < 5 years	34 27.4%	30 24.6%	44 27.7%	68 29.1%	0 0%	0 0%	176 26.5%
5 - 8 years	32 25.8%	32 26.2%	31 19.5%	49 20.9%	0 0%	0 0%	144 21.7%
9 - 17 years	29 23.4%	30 24.6%	30 18.9%	42 17.9%	0 0%	0 0%	131 19.7%
Sex: Female, Male (Count of Participants)
Female	51 41.1%	61 50%	82 51.6%	114 48.7%	4 30.8%	6 46.2%	318 47.8%
Male	73 58.9%	61 50%	77 48.4%	120 51.3%	9 69.2%	7 53.8%	347 52.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 1.6%	0 0%	0 0%	2 0.9%	0 0%	0 0%	4 0.6%
Asian	1 0.8%	2 1.6%	0 0%	3 1.3%	0 0%	0 0%	6 0.9%
Native Hawaiian or Other Pacific Islander	0 0%	3 2.5%	2 1.3%	5 2.1%	0 0%	1 7.7%	11 1.7%
Black or African American	22 17.7%	28 23%	40 25.2%	58 24.8%	2 15.4%	0 0%	150 22.6%
White	92 74.2%	81 66.4%	108 67.9%	157 67.1%	9 69.2%	11 84.6%	458 68.9%
More than one race	4 3.2%	3 2.5%	8 5%	7 3%	2 15.4%	1 7.7%	25 3.8%
Unknown or Not Reported	3 2.4%	5 4.1%	1 0.6%	2 0.9%	0 0%	0 0%	11 1.7%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Immediate Unsolicited Adverse Events (AEs) After Any Vaccination
Description	An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the case report book (CRB) in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs includes both serious (SAEs) and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. All participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurred during that time were recorded as immediate unsolicited AEs in the CRB.
Time Frame	Within 30 minutes after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population which included participants who had received at least one dose of the study vaccines.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	122	121	158	234	13	13
Count of Participants [Participants]	0 0%	0 0%	1 0.6%	0 0%	0 0%	0 0%

2. Primary Outcome

Title	Number of Participants With Unsolicited Adverse Events After Any Vaccination
Description	An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the CRB in terms of diagnosis and/or onset window post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. Adverse reactions (ARs) were AEs related to vaccination. An injection site reaction was an AR at and around the injection site. Systemic AEs were all AEs that were not injection or administration site reactions.
Time Frame	Within 28 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS population.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	122	121	158	234	13	13
Unsolicited AE	46 37.1%	46 37.7%	53 33.3%	80 34.2%	11 84.6%	12 92.3%
Unsolicited non-serious AR	4 3.2%	8 6.6%	8 5%	10 4.3%	1 7.7%	3 23.1%
Unsolicited non-serious injection site AR	0 0%	3 2.5%	0 0%	0 0%	0 0%	1 7.7%
Unsolicited non-serious systemic AE	46 37.1%	45 36.9%	52 32.7%	80 34.2%	11 84.6%	12 92.3%
Unsolicited non-serious systemic AR	4 3.2%	5 4.1%	8 5%	10 4.3%	1 7.7%	2 15.4%

3. Primary Outcome

Title	Number of Participants With Serious Adverse Events (SAEs) After Any Vaccination
Description	An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event. An SAE which caused death of the participant was considered as fatal SAE. Adverse events of special interest (AESIs) were defined as SAEs which included new onset of Guillain-Barré syndrome, encephalitis/myelitis (including transverse myelitis), Bell's palsy, convulsions, optic neuritis, and brachial neuritis.
Time Frame	From Day 0 up to 6 months (i.e. 180 days) post last vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS population.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	122	121	158	234	13	13
SAE	0 0%	0 0%	2 1.3%	0 0%	0 0%	1 7.7%
Fatal SAE	0 0%	0 0%	0 0%	0 0%	0 0%	0 0%
AESI	0 0%	0 0%	1 0.6%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Number of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	Anti-influenza antibodies were measured by hemagglutination inhibition (HAI) assay for strains A/H1N1, A/H3N2, B/Victoria and B/Yamagata lineage. Seroconversion: defined as either HAI titer <10(1/dilution) at Day 0 and post-vaccination titer greater than or equal to (>=)40(1/dilution) at Day 28, or HAI titer >=10(1/dilution) at Day 0 and >=4-fold increase in HAI titer (1/dilution) at Day 28. Data for this Outcome Measure (OM) was planned to be collected and reported for dose level (QIV-HD 30μg and 45μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to complex study design and analysis of doses and age groups, QIV-SD group participants, who matched to participants in QIV-HD 30μg and 45μg dose formulations groups (who were 9 through 17 years old and shared matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on immunogenicity analysis set (IAS) population which included randomized participants who received 1 dose or 2 doses of study vaccine and had a post-vaccination blood sample. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4a: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 4b: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 4c: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 30 μg.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 45 μg.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 60 μg.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	40	41	157	13	13
A/H1N1	72 58.1%	71 58.2%	107 67.3%	26 11.1%	24 184.6%	98 753.8%	8 1.2%	11 NaN
A/H3N2	63 50.8%	79 64.8%	102 64.2%	18 7.7%	20 153.8%	71 546.2%	8 1.2%	12 NaN
B/Victoria	84 67.7%	94 77%	117 73.6%	28 12%	30 230.8%	111 853.8%	6 0.9%	12 NaN
B/Yamagata	79 63.7%	85 69.7%	120 75.5%	26 11.1%	31 238.5%	117 900%	8 1.2%	1 NaN

5. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. Data for this OM was planned to be collected and reported for dose level (QIV-HD 30 μg and QIV-HD 45 μg) matched separate groups for QIV-SD (Groups 4a, 4b and 4c), instead of pooled QIV-SD arm. Due to the complex study design and analysis of the dose formulation and age groups in the study, QIV-SD group participants, who matched to participants in the QIV-HD 30 μg and QIV-HD 45 μg dose formulations groups (who were 9 through 17 years old and shared a matching age group with QIV-SD control group), included in Groups 4a, 4b and 4c in this OM might be counted in more than once in QIV-SD arms for different dose levels, as applicable.
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4a: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 4b: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 4c: QIV-SD, 15 μg, (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 30 μg.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 45 μg.	Participants from US (aged 6 months to 17 years) received 15 μg QIV-SD, IM and were restricted for comparison to relevant experimental study group QIV-HD 60 μg.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	40	41	157	13	13
A/H1N1	673	676	834	698	791	618	59.7	604
A/H3N2	518	781	770	314	441	307	66.4	604
B/Victoria	378	432	494	296	468	310	56.6	1244
B/Yamagata	723	720	877	706	727	580	75.8	21.8

6. Primary Outcome

Title	Geometric Mean Titer Ratios (GMTRs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	GMTs of anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage, and B Yamagata lineage. GMTRs were calculated as the ratio of GMTs post-vaccination and pre-vaccination.
Time Frame	Day 0 (pre-vaccination), Day 28 (post any vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
A/H1N1: Day 28/Day 0	8.55	10.0	16.3	10.1	1.41	4.76
A/H3N2: Day 28/Day 0	6.42	9.35	10.3	4.61	1.41	15.5
B/Victoria: Day 28/Day 0	10.7	11.7	16.7	11.0	1.37	11.0
B/Yamagata: Day 28/Day 0	9.28	11.4	18.1	9.77	1.71	0.944

7. Primary Outcome

Title	Number of Participants With Neutralization Antibody Titers >= 40 (1/Dilution) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	GMT was measured for each influenza strain using HAI assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
A/H1N1: Day 28	113 91.1%	110 90.2%	142 89.3%	198 84.6%	0 0%	7 53.8%
A/H3N2: Day 28	111 89.5%	110 90.2%	139 87.4%	198 84.6%	0 0%	9 69.2%
B/Victoria: Day 28	112 90.3%	108 88.5%	140 88.1%	202 86.3%	0 0%	9 69.2%
B/Yamagata: Day 28	115 92.7%	109 89.3%	142 89.3%	215 91.9%	1 7.7%	1 7.7%

8. Primary Outcome

Title	Geometric Mean Titers of Influenza Antibodies (Measured by Seroneutralization [SN] Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	GMT was measured for each influenza strain using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage.
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
A/H1N1	6589	6213	7045	4948	33.8	234
A/H3N2	641	921	884	411	54.4	188
B/Victoria	500	605	628	378	6.05	57.9
B/Yamagata	1147	1159	1254	846	17.6	17.4

9. Primary Outcome

Title	Geometric Mean Titers Ratio of Influenza Antibodies (Measured by Seroneutralization Assay) Following Vaccination With Either High-Dose Quadrivalent Influenza Vaccine or Standard-Dose Quadrivalent Influenza Vaccine or Adjuvanted Trivalent Influenza Vaccine
Description	GMTRs of anti-influenza antibodies were measured using SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage and B/Yamagata lineage. GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.
Time Frame	Day 0 (pre-vaccination), Day 28 (post any vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
A/H1N1: Day 28/Day 0	11.3	18.8	29.1	14.5	2.38	7.12
A/H3N2: Day 28/Day 0	3.60	5.20	5.54	2.66	1.04	2.81
B/Victoria: Day 28/Day 0	12.4	15.4	19.9	12.7	1.03	10.5
B/Yamagata: Day 28/Day 0	9.75	11.5	14.1	8.49	1.16	1.10

10. Primary Outcome

Title	Number of Participants With Neutralization Antibody Titers Above Pre-Defined Thresholds
Description	Neutralizing Antibody titer was measured for each influenza strain with SN assay method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage at pre-defined thresholds of >=20, >=40 and >=80 (1/dilution).
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
A/H1N1: >=20 (1/dilution)	112 90.3%	112 91.8%	147 92.5%	208 88.9%	13 100%	11 84.6%
A/H1N1: >=40 (1/dilution)	112 90.3%	112 91.8%	147 92.5%	202 86.3%	12 92.3%	11 84.6%
A/H1N1: >=80 (1/dilution)	111 89.5%	111 91%	146 91.8%	201 85.9%	11 84.6%	11 84.6%
A/H3N2: >=20 (1/dilution)	113 91.1%	111 91%	142 89.3%	214 91.5%	13 100%	11 84.6%
A/H3N2: >=40 (1/dilution)	111 89.5%	111 91%	141 88.7%	208 88.9%	13 100%	11 84.6%
A/H3N2: >=80 (1/dilution)	107 86.3%	107 87.7%	138 86.8%	190 81.2%	11 84.6%	11 84.6%
B/Victoria: >=20 (1/dilution)	110 88.7%	108 88.5%	143 89.9%	201 85.9%	9 69.2%	11 84.6%
B/Victoria: >=40 (1/dilution)	108 87.1%	104 85.2%	136 85.5%	195 83.3%	8 61.5%	11 84.6%
B/Victoria: >=80 (1/dilution)	99 79.8%	99 81.1%	128 80.5%	181 77.4%	6 46.2%	11 84.6%
B/Yamagata: >=20 (1/dilution)	111 89.5%	112 91.8%	146 91.8%	213 91%	13 100%	10 76.9%
B/Yamagata: >=40 (1/dilution)	111 89.5%	108 88.5%	145 91.2%	208 88.9%	9 69.2%	6 46.2%
B/Yamagata: >=80 (1/dilution)	110 88.7%	103 84.4%	140 88.1%	201 85.9%	7 53.8%	2 15.4%

11. Primary Outcome

Title	Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer
Description	Neutralizing Antibody titer was measured for each influenza strain with SN method for 4 strains: A/H1N1, A/H3N2, B/Victoria lineage, and B/Yamagata lineage. 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / pre-vaccination computed value.
Time Frame	Day 28 post any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the IAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	118	115	156	227	13	13
2-Fold Rise: A/H1N1	80 64.5%	83 68%	118 74.2%	168 71.8%	6 46.2%	10 76.9%
4-Fold Rise: A/H1N1	65 52.4%	70 57.4%	104 65.4%	141 60.3%	5 38.5%	9 69.2%
2-Fold Rise: A/H3N2	69 55.6%	77 63.1%	110 69.2%	111 47.4%	2 15.4%	7 53.8%
4-Fold Rise: A/H3N2	44 35.5%	51 41.8%	72 45.3%	61 26.1%	0 0%	3 23.1%
2-Fold Rise: B/Victoria	95 76.6%	99 81.1%	131 82.4%	185 79.1%	2 15.4%	11 84.6%
4-Fold Rise: B/Victoria	80 64.5%	88 72.1%	113 71.1%	158 67.5%	0 0%	10 76.9%
2-Fold Rise: B/Yamagata	84 67.7%	95 77.9%	127 79.9%	187 79.9%	4 30.8%	3 23.1%
4-Fold Rise: B/Yamagata	71 57.3%	81 66.4%	109 68.6%	142 60.7%	1 7.7%	0 0%

12. Primary Outcome

Title	Number of Participants With Solicited Injection Site Reactions
Description	A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited injection site reactions included tenderness/pain, erythema, swelling, induration and bruising.
Time Frame	Within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	122	119	158	232	13	13
Injection site tenderness/pain	81 65.3%	84 68.9%	100 62.9%	116 49.6%	6 46.2%	5 38.5%
Injection site erythema	31 25%	30 24.6%	40 25.2%	48 20.5%	5 38.5%	8 61.5%
Injection site swelling	17 13.7%	15 12.3%	34 21.4%	23 9.8%	2 15.4%	2 15.4%
Injection site induration	21 16.9%	18 14.8%	26 16.4%	22 9.4%	4 30.8%	5 38.5%
Injection site bruising	10 8.1%	10 8.2%	13 8.2%	16 6.8%	1 7.7%	2 15.4%

13. Primary Outcome

Title	Number of Participants With Solicited Systemic Reactions After Any Vaccination
Description	A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included fever, vomiting, crying abnormal, drowsiness, appetite loss and irritability. Fever was planned to be evaluated for the whole population where as, the other events (vomiting, crying abnormal, drowsiness, appetite lost, and irritability) were planned to be evaluated only in the participants aged 6 months to <36 months.
Time Frame	Within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS population. Here, 'number analyzed' = number of participants with available data for each specified category.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)	Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)	Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	122	121	158	234	13	13
Fever	5 4%	6 4.9%	15 9.4%	11 4.7%	5 38.5%	6 46.2%
Vomiting	1 0.8%	2 1.6%	7 4.4%	11 4.7%	5 38.5%	7 53.8%
Crying abnormal	11 8.9%	9 7.4%	10 6.3%	20 8.5%	6 46.2%	9 69.2%
Drowsiness	14 11.3%	11 9%	12 7.5%	17 7.3%	5 38.5%	5 38.5%
Appetite lost	6 4.8%	10 8.2%	15 9.4%	20 8.5%	11 84.6%	11 84.6%
Irritability	14 11.3%	13 10.7%	18 11.3%	23 9.8%	6 46.2%	12 92.3%

14. Primary Outcome

Title	Number of Participants With Solicited Systemic Reactions After Any Vaccination: Participants Aged >36 Months
Description	A solicited reaction was an expected adverse reaction (sign or symptom) observed and reported under the conditions (nature and onset) prelisted (i.e., solicited) in the CRB and considered as related to the administered vaccination. Solicited systemic reactions included: headache, malaise, myalgia and shivering.
Time Frame	Within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the SafAS population. Here, "overall number of participants analyzed"= participants evaluable for this outcome measure. Data not collected and reported for Groups 5 and 6 because none of the participants in both groups lies in the age group of >36 months.

Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)	Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)	Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)	Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.	Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
Measure Participants	93	89	104	158
Headache	18 14.5%	18 14.8%	22 13.8%	21 9%
Malaise	16 12.9%	28 23%	27 17%	32 13.7%
Myalgia	29 23.4%	30 24.6%	32 20.1%	42 17.9%
Shivering	1 0.8%	8 6.6%	8 5%	6 2.6%

Adverse Events

Time Frame	AEs were collected from Day 0 (post-vaccination) up to 28 days after last vaccination. Solicited Reaction (SR) data were collected up to Day 7 after any vaccination. SAE data were collected throughout the study (up to 180 days after last vaccination).
Adverse Event Reporting Description	An SR was an AE that was prelisted (i.e., solicited) in the CRB and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the CRB in terms of diagnosis and/or onset window post-vaccination. Analysis was performed on SafAS population.
Arm/Group Title	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)		Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)		Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)		Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)		Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)		Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
Arm/Group Description	Participants from US (aged 6 months to 17 years) received single injection of 30 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.		Participants from US (aged 6 months to 17 years) received single injection of 45 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.		Participants from US (aged 6 months to 17 years) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.		Pooled arm consisted of participants who were from US aged 6 months to 17 years, randomized to Groups 1, 2 and 3 and received single injection of 15 μg unadjuvanted QIV-SD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.		Participants from Canada (aged 6 to <24 months) received single injection of 60 μg QIV-HD, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.		Participants from Canada (aged 6 to <24 months) received single injection of 7.5 μg adjuvanted TIV, IM at Day 0. Participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered at Day 28.
All Cause Mortality
	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)		Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)		Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)		Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)		Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)		Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/122 (0%)		0/121 (0%)		0/158 (0%)		0/234 (0%)		0/13 (0%)		0/13 (0%)
Serious Adverse Events
	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)		Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)		Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)		Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)		Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)		Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/122 (0%)		0/121 (0%)		2/158 (1.3%)		0/234 (0%)		0/13 (0%)		1/13 (7.7%)
Infections and infestations
Ear Infection	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Respiratory Syncytial Virus Infection	0/122 (0%)	0	0/121 (0%)	0	1/158 (0.6%)	1	0/234 (0%)	0	0/13 (0%)	0	0/13 (0%)	0
Nervous system disorders
Febrile Convulsion	0/122 (0%)	0	0/121 (0%)	0	1/158 (0.6%)	1	0/234 (0%)	0	0/13 (0%)	0	0/13 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1: QIV-HD 30 μg (US: 6 Months to 17 Years)		Group 2: QIV-HD 45 μg (US: 6 Months to 17 Years)		Group 3: QIV-HD, 60 μg (US: 6 Months to 17 Years)		Group 4: Pooled QIV-SD, 15 μg (US: 6 Months to 17 Years)		Group 5: QIV-HD, 60 μg (Canada: 6 to <24 Months)		Group 6: Adjuvanted TIV (Canada: 6 to <24 Months)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	101/122 (82.8%)		100/121 (82.6%)		118/158 (74.7%)		165/234 (70.5%)		13/13 (100%)		13/13 (100%)
Blood and lymphatic system disorders
Anaemia	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Ear and labyrinth disorders
Ear Pain	0/122 (0%)	0	1/121 (0.8%)	1	0/158 (0%)	0	1/234 (0.4%)	1	0/13 (0%)	0	1/13 (7.7%)	1
Gastrointestinal disorders
Abdominal Pain	0/122 (0%)	0	2/121 (1.7%)	2	0/158 (0%)	0	1/234 (0.4%)	1	1/13 (7.7%)	2	0/13 (0%)	0
Diarrhoea	5/122 (4.1%)	5	5/121 (4.1%)	6	9/158 (5.7%)	10	12/234 (5.1%)	13	1/13 (7.7%)	1	4/13 (30.8%)	8
Oral Mucosal Eruption	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Teething	2/122 (1.6%)	2	1/121 (0.8%)	1	1/158 (0.6%)	1	1/234 (0.4%)	2	0/13 (0%)	0	1/13 (7.7%)	1
Vomiting	10/122 (8.2%)	12	10/121 (8.3%)	10	12/158 (7.6%)	13	15/234 (6.4%)	16	5/13 (38.5%)	9	7/13 (53.8%)	9
General disorders
Chills	1/122 (0.8%)	1	8/121 (6.6%)	8	8/158 (5.1%)	8	6/234 (2.6%)	6	0/13 (0%)	0	0/13 (0%)	0
Crying	11/122 (9%)	12	9/121 (7.4%)	10	10/158 (6.3%)	12	20/234 (8.5%)	24	6/13 (46.2%)	9	9/13 (69.2%)	10
Influenza Like Illness	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Injection Site Bruising	10/122 (8.2%)	10	11/121 (9.1%)	11	13/158 (8.2%)	14	16/234 (6.8%)	16	1/13 (7.7%)	1	2/13 (15.4%)	2
Injection Site Erythema	31/122 (25.4%)	32	30/121 (24.8%)	32	40/158 (25.3%)	44	48/234 (20.5%)	52	5/13 (38.5%)	7	8/13 (61.5%)	9
Injection Site Induration	21/122 (17.2%)	22	19/121 (15.7%)	20	26/158 (16.5%)	27	22/234 (9.4%)	24	4/13 (30.8%)	5	5/13 (38.5%)	6
Injection Site Pain	81/122 (66.4%)	89	84/121 (69.4%)	96	100/158 (63.3%)	111	116/234 (49.6%)	126	6/13 (46.2%)	8	5/13 (38.5%)	6
Injection Site Swelling	17/122 (13.9%)	17	15/121 (12.4%)	17	34/158 (21.5%)	35	23/234 (9.8%)	25	2/13 (15.4%)	2	2/13 (15.4%)	2
Injection Site Warmth	0/122 (0%)	0	1/121 (0.8%)	1	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Malaise	16/122 (13.1%)	16	28/121 (23.1%)	29	27/158 (17.1%)	27	32/234 (13.7%)	33	0/13 (0%)	0	0/13 (0%)	0
Pyrexia	11/122 (9%)	12	10/121 (8.3%)	11	19/158 (12%)	22	24/234 (10.3%)	25	9/13 (69.2%)	15	9/13 (69.2%)	17
Infections and infestations
Bronchiolitis	1/122 (0.8%)	1	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Bronchitis	1/122 (0.8%)	1	0/121 (0%)	0	1/158 (0.6%)	1	0/234 (0%)	0	3/13 (23.1%)	3	0/13 (0%)	0
Conjunctivitis	1/122 (0.8%)	1	1/121 (0.8%)	1	2/158 (1.3%)	2	2/234 (0.9%)	2	1/13 (7.7%)	1	0/13 (0%)	0
Ear Infection	2/122 (1.6%)	2	0/121 (0%)	0	1/158 (0.6%)	1	3/234 (1.3%)	3	3/13 (23.1%)	4	3/13 (23.1%)	4
Gastroenteritis	1/122 (0.8%)	1	1/121 (0.8%)	1	0/158 (0%)	0	1/234 (0.4%)	1	3/13 (23.1%)	3	1/13 (7.7%)	1
Nasopharyngitis	4/122 (3.3%)	4	4/121 (3.3%)	4	8/158 (5.1%)	8	5/234 (2.1%)	5	7/13 (53.8%)	9	7/13 (53.8%)	13
Otitis Media	0/122 (0%)	0	1/121 (0.8%)	1	2/158 (1.3%)	2	2/234 (0.9%)	2	1/13 (7.7%)	1	0/13 (0%)	0
Pharyngitis	0/122 (0%)	0	0/121 (0%)	0	1/158 (0.6%)	1	0/234 (0%)	0	2/13 (15.4%)	2	2/13 (15.4%)	2
Sinusitis	0/122 (0%)	0	1/121 (0.8%)	1	0/158 (0%)	0	1/234 (0.4%)	1	1/13 (7.7%)	1	0/13 (0%)	0
Upper Respiratory Tract Infection	5/122 (4.1%)	5	0/121 (0%)	0	6/158 (3.8%)	6	8/234 (3.4%)	8	0/13 (0%)	0	1/13 (7.7%)	1
Injury, poisoning and procedural complications
Tongue Injury	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Metabolism and nutrition disorders
Decreased Appetite	6/122 (4.9%)	6	10/121 (8.3%)	11	15/158 (9.5%)	18	20/234 (8.5%)	24	11/13 (84.6%)	14	11/13 (84.6%)	14
Musculoskeletal and connective tissue disorders
Myalgia	29/122 (23.8%)	33	30/121 (24.8%)	31	33/158 (20.9%)	34	43/234 (18.4%)	45	0/13 (0%)	0	0/13 (0%)	0
Nervous system disorders
Aphonia	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	1/13 (7.7%)	1	0/13 (0%)	0
Headache	18/122 (14.8%)	19	19/121 (15.7%)	19	22/158 (13.9%)	22	22/234 (9.4%)	22	0/13 (0%)	0	0/13 (0%)	0
Somnolence	14/122 (11.5%)	15	11/121 (9.1%)	12	12/158 (7.6%)	17	18/234 (7.7%)	21	5/13 (38.5%)	6	5/13 (38.5%)	7
Psychiatric disorders
Insomnia	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	1/13 (7.7%)	1	1/13 (7.7%)	1
Irritability	14/122 (11.5%)	16	13/121 (10.7%)	15	18/158 (11.4%)	24	23/234 (9.8%)	27	7/13 (53.8%)	11	12/13 (92.3%)	19
Sleep Terror	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Respiratory, thoracic and mediastinal disorders
Cough	17/122 (13.9%)	17	19/121 (15.7%)	22	15/158 (9.5%)	17	30/234 (12.8%)	30	2/13 (15.4%)	4	1/13 (7.7%)	1
Nasal Congestion	2/122 (1.6%)	2	8/121 (6.6%)	8	3/158 (1.9%)	3	6/234 (2.6%)	6	1/13 (7.7%)	1	0/13 (0%)	0
Rhinorrhoea	7/122 (5.7%)	7	6/121 (5%)	6	4/158 (2.5%)	7	13/234 (5.6%)	13	0/13 (0%)	0	1/13 (7.7%)	1
Skin and subcutaneous tissue disorders
Dermatitis Diaper	1/122 (0.8%)	1	0/121 (0%)	0	2/158 (1.3%)	3	3/234 (1.3%)	3	1/13 (7.7%)	1	1/13 (7.7%)	1
Erythema	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Petechiae	0/122 (0%)	0	0/121 (0%)	0	0/158 (0%)	0	0/234 (0%)	0	0/13 (0%)	0	1/13 (7.7%)	1
Rash	0/122 (0%)	0	2/121 (1.7%)	2	0/158 (0%)	0	1/234 (0.4%)	1	2/13 (15.4%)	2	1/13 (7.7%)	1

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable participant matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.