Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2016-2017 Formulations

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02908269

Enrollment

180

Registered

2016-09-20

Start date

2016-09-15

Completion date

2016-12-09

Last updated

2022-03-29

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Influenza

Keywords

Influenza, Fluzone® Quadrivalent, Influenza Vaccine (2016-2017 formulation), Fluzone® High-Dose, Influenza Vaccine (2016-2017 formulation)

Brief summary

The aim of the study was to describe the safety and immunogenicity of the 2016-2017 formulations of Fluzone Quadrivalent vaccine in children 3 to \< 9 years of age and in adults 18 to \< 65 years or age, and of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥65 years of age. Primary Observational Objectives * To describe the safety of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in children 3 to \< 9 years of age and adults 18 to \< 65 years of age, and the safety of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age. Observational Objectives: * To describe the immunogenicity of the 2016-2017 formulation of Fluzone Quadrivalent vaccine in children 3 to \< 9 years of age and adults 18 to \< 65 years of age, and the immunogenicity of the 2016-2017 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age. * To submit available sera from approximately 90 participants (30 participants 3 to \< 9 years of age and 30 participants 18 to \< 65 years of age who receive Fluzone Quadrivalent vaccine, and 30 participants ≥ 65 years of age who receive Fluzone High-Dose vaccine) to Center for Biologics Evaluation and Research (CBER) for further analysis by the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the Food and Drug Administration (FDA) to support formulation recommendations for subsequent influenza vaccines.

Detailed description

All participants received a 0.5-mL intramuscular dose of their assigned vaccine at Visit 1. For participants 3 to \< 9 years of age for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of Fluzone Quadrivalent vaccine (of the same volume) was administered during Visit 2. Solicited adverse reaction (AR) information was collected for 7 days after vaccination. Unsolicited non-serious adverse event (AE) and serious adverse event (SAE) information was collected from Visit 1 to Visit 2 or from Visit 1 to Visit 3 for those participants receiving 2 doses of study vaccine. Immunogenicity was evaluated in all participants prior to vaccination on Day 0 (Visit 1) and after the final vaccination on Day 28 for 3 to \< 9 year olds and Day 21 days for adults 18 years and older.

Interventions

BIOLOGICALFluzone Quadrivalent vaccine, 2016-2017 formulation, No Preservative

0.5 mL, Intramuscular

BIOLOGICALFluzone High-Dose, vaccine, 2016-2017 formulation

0.5 mL, Intramuscular

Study design

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

3 Years to No maximum

Healthy volunteers

Yes

Inclusion criteria

* Aged 3 to \<9 years or adult aged ≥ 18 years on the day of first study vaccination (study product administration) . * Informed consent form had been signed and dated by participants ≥ 18 years of age. * Assent form had been signed and dated by participants 7 to \<9 years of age, and informed consent form (ICF) has been signed and dated by parent(s) or guardian(s) for participants 3 to \<9 years of age. * Participant and parent/guardian (of participants 3 to \<9 years of age) were able to attend all scheduled visits and to comply with all trial procedures.

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 and until at least 4 weeks after vaccination. To be considered of non-childbearing potential, a female must be pre-menarche, or post-menopausal for at least 1 year, or surgically sterile. * Participation at the time of study enrollment (or in the 30 days preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device, or medical procedure. * Receipt of any vaccine in the 30 days preceding the first trial vaccination, or planned receipt of any vaccine before Visit 2 for participants receiving 1 dose of influenza vaccine or Visit 3 for participants receiving 2 doses of influenza vaccine. * Previous vaccination against influenza (in the 2016-2017 influenza season) with either the trial vaccine or another vaccine. * 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 vaccine used in the trial or to a vaccine containing any of the same substances. * Thrombocytopenia, which may be a contraindication for intramuscular vaccination, at the discretion of the Investigator. * Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular vaccination. * 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, is at a stage where it might interfere with trial conduct or completion. * Moderate or severe acute illness/infection (according to Investigator judgment) on the day of planned vaccination or febrile illness (temperature ≥100.4°F \[38.0°C\]). A prospective participant should not be included in the study until the condition has resolved or the febrile event has subsided. * Identified as an Investigator or employee of the Investigator or study center with direct involvement in the proposed study (participants ≥18 years of age) or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study (all participants). * History of serious adverse reaction to any influenza vaccine. * 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 developmental delay (at the discretion of the Investigator), neurologic disorder, or seizure disorder. * Known seropositivity for human immunodeficiency virus, hepatitis B, or hepatitis C.

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Within 7 days after any vaccination	Solicited injection site reactions: Pain (Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities), erythema & swelling (Grade 1: \>0 to \<25 mm;Grade 2: ≥ 25 to \< 50 mm; Grade 3: ≥ 50 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported.
Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Within 7 days after any vaccination	Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant; prevents daily activity), erythema & swelling (Grade 1: ≥ 25 to ≤ 50 mm; Grade 2: ≥ 51 to ≤ 100 mm; Grade 3: \>100 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported.

Secondary

Measure	Time frame	Description
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 3: ≥ 65 Years)	Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 3 strains: H1N1, H3N2, Victoria lineage.
Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 1: 3 to < 9 Years)	Day 0 (pre-vaccination) and 28 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. Seroprotection was defined as an antibody titer ≥40 (1/dilution \[dil\]) at pre-vaccination and at post-final vaccination.
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Day 0 (pre-vaccination) and 28 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage.
Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 3: ≥ 65 Years)	Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using HAI assay for 3 strains: H1N1, H3N2, Victoria lineage. Seroprotection was defined as an antibody titer ≥ 40 (1/dilution \[dil\]) at pre-vaccination and at post-final vaccination.
Number of Participants With Seroprotection to Influenza Vaccine Antigens (Group 2: 18 to < 65 Years)	Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using HAI assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage. Seroprotection was defined as an antibody titer ≥ 40 (1/dilution \[dil\]) at pre-vaccination and at post-final vaccination.
Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 2: 18 to < 65 Years)	Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination)	Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage.

Countries

United States

Participant flow

Recruitment details

Study participants were enrolled in 2 centers in the United States from 15 September 2016 to 28 September 2016.

Pre-assignment details

A total of 180 participants (60 for each group) were enrolled and vaccinated in the study.

Participants by arm

Arm	Count
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years Participants aged 3 to \< 9 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended per ACIP guidance, a second dose of Fluzone Quadrivalent vaccine was administered at Day 28.	60
Fluzone Quadrivalent Vaccine Group 2: 18 to < 65 Years Participants aged 18 to \< 65 years received one 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	60
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years Participants aged ≥ 65 years received one 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.	60
Total	180

Baseline characteristics

Characteristic	Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Fluzone Quadrivalent Vaccine Group 2: 18 to < 65 Years	Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Total
Age, Continuous	6.03 years STANDARD_DEVIATION 1.61	42.2 years STANDARD_DEVIATION 12.9	72.6 years STANDARD_DEVIATION 6.19	40.3 years STANDARD_DEVIATION 28.5
Region of Enrollment United States	60 participants	60 participants	60 participants	180 participants
Sex: Female, Male Female	26 Participants	42 Participants	45 Participants	113 Participants
Sex: Female, Male Male	34 Participants	18 Participants	15 Participants	67 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	0 / 60	0 / 60	0 / 60
other Total, other adverse events	35 / 60	33 / 60	25 / 60
serious Total, serious adverse events	1 / 60	0 / 60	2 / 60

Outcome results

Primary

Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)

Solicited injection site reactions: Pain (Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities), erythema & swelling (Grade 1: \>0 to \<25 mm;Grade 2: ≥ 25 to \< 50 mm; Grade 3: ≥ 50 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported.

Time frame: Within 7 days after any vaccination

Population: Analysis was performed using the Safety Analysis Set, which included all participants who received the study vaccine. Number of participants analyzed corresponds to participants with available data for the listed solicited reaction.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Injection site pain	18 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade 3 Injection site pain	1 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Injection site erythema	6 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade3 Injection site erythema	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Injection site swelling	7 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade3 Injection site swelling	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Fever	3 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade 3 Fever	1 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Headache	9 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade 3 Headache	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Malaise	15 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade 3 Malaise	1 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Any Myalgia	12 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 1 (3 to < 9 Years of Age)	Grade 3 Myalgia	0 Participants

Primary

Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)

Solicited injection site reactions: Pain (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant; prevents daily activity), erythema & swelling (Grade 1: ≥ 25 to ≤ 50 mm; Grade 2: ≥ 51 to ≤ 100 mm; Grade 3: \>100 mm). Solicited systemic reactions: Fever (Grade 1: ≥ 38.0 degrees Celsius to ≤ 38.4 degrees Celsius, Grade 2: ≥ 38.5 degrees Celsius to ≤ 38.9 degrees Celsius, Grade 3: ≥ 39.0 degrees Celsius), headache, malaise & myalgia (Grade 1: no interference with activity, Grade 2: some interference, Grade 3: significant interference). Number of participants with any solicited injection-site & systemic reactions are reported; number of participants with Grade 3 solicited injection-site & systemic reactions are also reported.

Time frame: Within 7 days after any vaccination

Population: Analysis was performed on safety analysis set.

Arm	Measure	Group	Value (COUNT_OF_PARTICIPANTS)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site pain	28 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Injection site pain	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site erythema	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade3 Injection site erythema	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site swelling	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade3 Injection site swelling	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Fever	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Fever	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Headache	11 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Headache	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Malaise	10 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Malaise	0 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Myalgia	15 Participants
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Myalgia	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Malaise	4 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site pain	12 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Fever	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Injection site pain	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Myalgia	11 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site erythema	3 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Headache	8 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade3 Injection site erythema	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Malaise	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Injection site swelling	1 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Headache	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade3 Injection site swelling	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Grade 3 Myalgia	0 Participants
Fluzone High-Dose Vaccine Group 3: ≥ 65 Years	Number of Participants Reporting Solicited Injection Site Reactions (Pain, Erythema, and Swelling) and Systemic Reactions (Fever, Headache, Malaise, Myalgia): Group 2 (18 to < 65 Years) and Group 3 (≥ 65 Years)	Any Fever	1 Participants

Secondary

Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)

Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage.

Time frame: Day 0 (pre-vaccination) and 28 days post-final vaccination (post-vaccination)

Population: Analysis was performed using the Per-protocol Analysis Set (PPAS), which included all participants who received study vaccine and had a valid post-vaccination serology result for at least 1 strain.

Arm	Measure	Group	Value (GEOMETRIC_MEAN)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Pre-Vaccination: A/H1N1	273 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Pre-Vaccination: A/H3N2	167 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Pre-Vaccination: B Victoria	111 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Pre-Vaccination: B Yamagata	170 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Post-Vaccination: A/H1N1	1232 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Post-Vaccination: A/H3N2	2495 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Post-Vaccination: B Victoria	1208 Titers (1/dilutions)
Fluzone Quadrivalent Vaccine Group 1: 3 to < 9 Years	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 1: 3 to < 9 Years)	Post-Vaccination: B Yamagata	1731 Titers (1/dilutions)

Secondary

Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies (Group 2: 18 to < 65 Years)

Anti-influenza antibodies were measured using hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, Victoria lineage, Yamagata lineage.

Time frame: Day 0 (pre-vaccination) and 21 days post-final vaccination (post-vaccination)