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

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03308825
• Collaborator: (none)
• Enrollment: 240
• Locations: 3
• Arms: 4
• Actual Duration (Months): 2.4
• Patients Per Site: 80
• Patients Per Site Per Month: 33.8

Study Details

Study Description

Brief Summary

The aim of the study was to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone Quadrivalent vaccine in children 6 months to < 9 years of age, and in adults 18 to < 65 years of age, and to describe the safety and immunogenicity of the 2017-2018 formulation of Fluzone High-Dose vaccine in adults ≥ 65 years of age.

Condition or Disease	Intervention/Treatment	Phase
Influenza; Flu	Biological: Fluzone Quadrivalent vaccine; Biological: Fluzone Quadrivalent vaccine; Biological: Fluzone High-Dose vaccine	Phase 4

Detailed Description

All participants received 1 intramuscular dose of their assigned vaccine during Visit 1. For participants, for whom 2 doses of influenza vaccine were recommended per Advisory Committee on Immunization Practices (ACIP) guidance, a second dose of the same volume as the first dose was administered during Visit 2 (28 days after Visit 1). Solicited adverse reaction (AR) information was collected for 7 days following each 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 (Day 28 post-final vaccination for participants 6 months to < 9 years of age and Day 21 post-vaccination for participants ≥ 18 years of age).

Study Design

• Study Type: Interventional
• Actual Enrollment: 240 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Multicenter, Open-label, Phase IV StudyMulticenter, Open-label, Phase IV Study
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of Fluzone® Quadrivalent and Fluzone® High-Dose, Influenza Vaccines, 2017-2018 Formulations
• Actual Study Start Date: Sep 11, 2017
• Actual Primary Completion Date: Nov 22, 2017
• Actual Study Completion Date: Nov 22, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1: 6 to < 36 Months Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Biological: Fluzone Quadrivalent vaccine; 0.25 mL, Intramuscular
Experimental: Group 2: 3 to < 9 Years Children 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, a second dose was administered on Day 28.	Biological: Fluzone Quadrivalent vaccine; 0.5 mL, Intramuscular
Experimental: Group 3: 18 to < 65 Years Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Biological: Fluzone Quadrivalent vaccine; 0.5 mL, Intramuscular
Experimental: Group 4: >= 65 Years Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.	Biological: Fluzone High-Dose vaccine; 0.5 mL, Intramuscular

Outcome Measures

Primary Outcome Measures

1. Number of Participants Reporting Solicited Injection Site (Tenderness/Pain, Erythema, Swelling) and Systemic Reactions (Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, Irritability): Group 1 (6 to < 36 Months) [Within 7 days after any vaccination]

   Solicited injection site reactions: Pain, Erythema and Swelling (Grade 3: Pain: cries when injected limb moved/ limb movement reduced, erythema and swelling >= 50 mm). Solicited systemic reactions: Fever, vomiting, abnormal crying, drowsiness, appetite lost, Irritability (Grade 3: Fever: >= 39.5 degrees Celsius [103.1 degree Fahrenheit {°F}], vomiting >= six episodes per 24 hours, abnormal crying : > 3 hours, drowsiness: sleeping most of the time or difficult to wake up, appetite lost: refuses >= 3 feeds/meals or refuses most feeds/meals, Irritability: Inconsolable).

2. Number of Participants Reporting Solicited Injection Site (Pain, Erythema, Swelling) and Systemic Reactions(Fever, Headache, Malaise, Myalgia): Group 2 (3 to < 9 Years), Group 3 (18 to < 65 Years) and Group 4(=< 65 Years) [Within 7 days after any vaccination]

   Solicited injection site reactions: Pain (Group 2: Grade 3: Incapacitating; Group 3 and 4: Grade 3: significant; prevents daily activity), erythema & swelling (Group 2: Grade 3: >= 50 mm, Group 3 and 4: Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 3: >= 39.0 degrees Celsius [102.2°F]), headache, malaise & myalgia (Grade 3: significant interference with daily activities).

3. Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [Day 0 (pre-vaccination) and Day 28 (post-vaccination)]

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

4. GMTs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [Day 0 (pre-vaccination) and Day 21 (post-vaccination)]

   Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4).

5. GMT Ratios (GMTRs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [Day 0 (pre-vaccination) and Day 28 (post-final vaccination)]

   GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage, measured using the HAI assay.

6. GMTRs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [Day 0 (pre-vaccination) and Day 21 (post-vaccination)]

   GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4), measured using the HAI assay.

7. Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [Day 0 (pre-vaccination) and Day 28 (post-vaccination)]

   Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroprotection was defined as antibody titer >=40 (1/ dilution) at pre-vaccination or at post-final vaccination.

8. Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [Day 0 (pre-vaccination) and Day 21 (post-vaccination)]

   Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroprotection was defined as antibody titer >= 40 (1/ dilution) at pre-vaccination or at post-final vaccination.

9. Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years) [Day 0 (pre-vaccination) and Day 28 (post-final vaccination)]

   Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.

10. Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years) [Day 0 (pre-vaccination) and Day 21 (post-vaccination)]

    Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged 6 months to < 9 years or ≥ 18 years on the day of first study vaccination (study product administration).

• For participants 6 to < 12 months of age, born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg (5.5 lbs).

• Informed consent form has been signed and dated by participants ≥ 18 years of age.

• Assent form was signed and dated by participants 7 to < 9 years of age, and informed consent form has been signed and dated by parent(s) or guardian(s) for participants 6 months to < 9 years of age.

• Participant and parent/guardian (of participants 6 months to < 9 years of age) were able to attend all scheduled visits and to comply with all study 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 study vaccination) or planned participation during the present study period in another clinical study investigating a vaccine, drug, medical device, or medical procedure. Note: Participants may be considered eligible for enrollment if no intervention for the other study occurred within the 30 days prior to the first study vaccination and none are planned before the participant would complete safety surveillance for the present study.

• Receipt of any vaccine in the 30 days preceding the first study 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 2017-2018 influenza season) with either study vaccine or another vaccine.

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

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

• Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to study vaccine or to a vaccine containing any of the same substances. Note: The list of vaccine components is included in the Prescribing Information for each study vaccine.

• 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, 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 planned vaccination or febrile illness (temperature ≥ 100.4 degree Fahrenheit [°F] [38.0 degrees Celsius {°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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi Pasteur Investigational Site 003	Council Bluffs	Iowa	United States	51503
2	Sanofi Pasteur Investigational Site 002	Bardstown	Kentucky	United States	40004
3	Sanofi Pasteur Investigational Site 001	Metairie	Louisiana	United States	70006

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur, a Sanofi Company

Study Documents (Full-Text)

• Study Protocol - Apr 24, 2017
• Statistical Analysis Plan - Nov 10, 2017

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03308825
• Other Study ID Numbers: GRC73; U1111-1183-5816
• First Posted: Oct 13, 2017
• Last Update Posted: Mar 29, 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
• Keywords provided by Sanofi Pasteur, a Sanofi Company: Influenza; Flu
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled in 3 centers in the United States from 11 September 2017 to 25 October 2017.
Pre-assignment Detail	A total of 240 participants were enrolled and vaccinated in the study.

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
Period Title: Overall Study
STARTED	59	61	60	60
COMPLETED	57	57	59	60
NOT COMPLETED	2	4	1	0

Baseline Characteristics

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years	Group 3: 18 to < 65 Years	Group 4: >= 65 Years	Total
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.	Total of all reporting groups
Overall Participants	59	61	60	60	240
Age (Count of Participants)
<=18 years	59 100%	61 100%	1 1.7%	0 0%	121 50.4%
Between 18 and 65 years	0 0%	0 0%	59 98.3%	0 0%	59 24.6%
>=65 years	0 0%	0 0%	0 0%	60 100%	60 25%
Sex: Female, Male (Count of Participants)
Female	25 42.4%	31 50.8%	46 76.7%	39 65%	141 58.8%
Male	34 57.6%	30 49.2%	14 23.3%	21 35%	99 41.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 5.1%	6 9.8%	0 0%	1 1.7%	10 4.2%
Not Hispanic or Latino	56 94.9%	55 90.2%	60 100%	59 98.3%	230 95.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	1 1.7%	1 0.4%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	29 49.2%	30 49.2%	16 26.7%	5 8.3%	80 33.3%
White	29 49.2%	25 41%	43 71.7%	53 88.3%	150 62.5%
More than one race	1 1.7%	6 9.8%	1 1.7%	1 1.7%	9 3.8%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Reporting Solicited Injection Site (Tenderness/Pain, Erythema, Swelling) and Systemic Reactions (Fever, Vomiting, Crying Abnormal, Drowsiness, Appetite Lost, Irritability): Group 1 (6 to < 36 Months)
Description	Solicited injection site reactions: Pain, Erythema and Swelling (Grade 3: Pain: cries when injected limb moved/ limb movement reduced, erythema and swelling >= 50 mm). Solicited systemic reactions: Fever, vomiting, abnormal crying, drowsiness, appetite lost, Irritability (Grade 3: Fever: >= 39.5 degrees Celsius [103.1 degree Fahrenheit {°F}], vomiting >= six episodes per 24 hours, abnormal crying : > 3 hours, drowsiness: sleeping most of the time or difficult to wake up, appetite lost: refuses >= 3 feeds/meals or refuses most feeds/meals, Irritability: Inconsolable).
Time Frame	Within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed using the Safety Analysis Set. Here, "Number analyzed" corresponds to participants with available data for each listed solicited reaction.

Arm/Group Title	Group 1: 6 to < 36 Months
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.
Measure Participants	59
Tenderness	16 27.1%
Tenderness : Grade 3	1 1.7%
Erythema	4 6.8%
Erythema : Grade 3	0 0%
Swelling	2 3.4%
Swelling : Grade 3	0 0%
Fever	6 10.2%
Fever : Grade 3	0 0%
Vomiting	2 3.4%
Vomiting : Grade 3	0 0%
Crying Abnormal	10 16.9%
Crying Abnormal : Grade 3	0 0%
Drowsiness	11 18.6%
Drowsiness : Grade 3	0 0%
Appetite Lost	7 11.9%
Appetite Lost : Grade 3	0 0%
Irritability	13 22%
Irritability : Grade 3	0 0%

2. Primary Outcome

Title	Number of Participants Reporting Solicited Injection Site (Pain, Erythema, Swelling) and Systemic Reactions(Fever, Headache, Malaise, Myalgia): Group 2 (3 to < 9 Years), Group 3 (18 to < 65 Years) and Group 4(=< 65 Years)
Description	Solicited injection site reactions: Pain (Group 2: Grade 3: Incapacitating; Group 3 and 4: Grade 3: significant; prevents daily activity), erythema & swelling (Group 2: Grade 3: >= 50 mm, Group 3 and 4: Grade 3: > 100 mm). Solicited systemic reactions: Fever (Grade 3: >= 39.0 degrees Celsius [102.2°F]), headache, malaise & myalgia (Grade 3: significant interference with daily activities).
Time Frame	Within 7 days after any vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed using Safety Analysis Set. Here, "Number analyzed" corresponds to participants with available data for each listed solicited reaction.

Arm/Group Title	Group 2: 3 to < 9 Years	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Arm/Group Description	Children 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, a second dose was administered on Day 28.	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
Measure Participants	61	60	60
Pain	25 42.4%	27 44.3%	20 33.3%
Pain: Grade 3	1 1.7%	1 1.6%	0 0%
Erythema	9 15.3%	0 0%	3 5%
Erythema : Grade 3	3 5.1%	0 0%	0 0%
Swelling	11 18.6%	1 1.6%	2 3.3%
Swelling : Grade 3	2 3.4%	0 0%	0 0%
Fever	1 1.7%	0 0%	1 1.7%
Fever : Grade 3	1 1.7%	0 0%	1 1.7%
Headache	2 3.4%	10 16.4%	6 10%
Headache : Grade 3	0 0%	1 1.6%	0 0%
Malaise	3 5.1%	5 8.2%	9 15%
Malaise: Grade 3	1 1.7%	1 1.6%	0 0%
Myalgia	11 18.6%	13 21.3%	17 28.3%
Myalgia : Grade 3	0 0%	1 1.6%	1 1.7%

3. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)
Description	Anti-influenza antibodies were measured using the hemagglutination inhibition (HAI) assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage.
Time Frame	Day 0 (pre-vaccination) and Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Per-Protocol Analysis Set (PPAS) included all participants who received at least 1dose of study vaccine, had a valid post-final vaccination serology result for at least 1 strain and did not have any major protocol deviations. Here, "Number analyzed" corresponds to participants with available data for each listed strain.

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.
Measure Participants	52	55
Pre-Vaccination: A/H1N1	19.9	306
Pre-Vaccination: A/H3N2	49.7	415
Pre-Vaccination: B Victoria	32.0	180
Pre-Vaccination: B Yamagata	43.5	334
Post-Final Vaccination: A/H1N1	450	1606
Post-Final Vaccination: A/H3N2	568	2370
Post-Final Vaccination: B Victoria	481	1668
Post-Final Vaccination: B Yamagata	698	2187

4. Primary Outcome

Title	GMTs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)
Description	Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4).
Time Frame	Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain and "0" in the number analyzed field signifies that none of the participants were analyzed, since the 2017-2018 formulation of Fluzone High-Dose vaccine did not contain the B Yagamata lineage strain.

Arm/Group Title	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Arm/Group Description	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
Measure Participants	56	59
Pre-Vaccination: A/H1N1	165	74.6
Pre-Vaccination: A/H3N2	231	194
Pre-Vaccination: B Victoria	276	215
Pre-Vaccination: B Yamagata	425
Post-Final Vaccination: A/H1N1	756	393
Post-Final Vaccination: A/H3N2	1128	864
Post-Final Vaccination: B Victoria	1117	644
Post-Final Vaccination: B Yamagata	1312

5. Primary Outcome

Title	GMT Ratios (GMTRs) of Influenza Vaccine Antibodies in Children: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)
Description	GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage, measured using the HAI assay.
Time Frame	Day 0 (pre-vaccination) and Day 28 (post-final vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain.

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.
Measure Participants	52	55
A/H1N1	17.6	5.05
A/H3N2	10.8	5.54
B Victoria	13.1	9.02
B Yamagata	14.0	6.46

6. Primary Outcome

Title	GMTRs of Influenza Vaccine Antibodies in Adults: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)
Description	GMTRs are the geometric means of the individual post-final vaccination/pre-vaccination titer ratios for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4), measured using the HAI assay.
Time Frame	Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain and "0" in the number analyzed field signifies that none of the participants were analyzed, since the 2017-2018 formulation of Fluzone High-Dose vaccine did not contain the B Yagamata lineage strain.

Arm/Group Title	Group 3: 18 to < 65 Years	Group 4: Adults >= 65 Years
Arm/Group Description	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults >= 65 years of age received an intramuscular 0.5-mL dose of Fluzone High-Dose vaccine on Day 0.
Measure Participants	56	59
A/H1N1	4.31	5.15
A/H3N2	4.44	4.45
B Victoria	4.05	2.96
B Yamagata	3.09

7. Primary Outcome

Title	Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)
Description	Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroprotection was defined as antibody titer >=40 (1/ dilution) at pre-vaccination or at post-final vaccination.
Time Frame	Day 0 (pre-vaccination) and Day 28 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain.

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.
Measure Participants	52	55
Pre-Vaccination: A/H1N1	15 25.4%	48 78.7%
Pre-Vaccination: A/H3N2	24 40.7%	46 75.4%
Pre-Vaccination: B Victoria	21 35.6%	44 72.1%
Pre-Vaccination: B Yamagata	31 52.5%	50 82%
Post-Final Vaccination: A/H1N1	51 86.4%	54 88.5%
Post-Final Vaccination: A/H3N2	50 84.7%	54 88.5%
Post-Final Vaccination: B Victoria	50 84.7%	54 88.5%
Post-Final Vaccination: B Yamagata	50 84.7%	55 90.2%

8. Primary Outcome

Title	Number of Participants With Seroprotection to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)
Description	Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroprotection was defined as antibody titer >= 40 (1/ dilution) at pre-vaccination or at post-final vaccination.
Time Frame	Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain and "0" in the number analyzed field signifies that none of the participants were analyzed, since the 2017-2018 formulation of Fluzone High-Dose vaccine did not contain the B Yagamata lineage strain.

Arm/Group Title	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Arm/Group Description	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
Measure Participants	56	59
Pre-Vaccination: A/H1N1	45 76.3%	40 65.6%
Pre-Vaccination: A/H3N2	48 81.4%	49 80.3%
Pre-Vaccination: B Victoria	48 81.4%	55 90.2%
Pre-Vaccination: B Yamagata	54 91.5%
Post-Final Vaccination: A/H1N1	55 93.2%	57 93.4%
Post-Final Vaccination: A/H3N2	55 93.2%	59 96.7%
Post-Final Vaccination: B Victoria	56 94.9%	58 95.1%
Post-Final Vaccination: B Yamagata	56 94.9%

9. Primary Outcome

Title	Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 1 (6 to < 36 Months) and Group 2 (3 to < 9 Years)
Description	Anti-influenza antibodies were measured using the HAI assay for 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage. Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.
Time Frame	Day 0 (pre-vaccination) and Day 28 (post-final vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain.

Arm/Group Title	Group 1: 6 to < 36 Months	Group 2: 3 to < 9 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.	Children 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, a second dose was administered on Day 28.
Measure Participants	52	55
A/H1N1	45 76.3%	28 45.9%
A/H3N2	42 71.2%	30 49.2%
B Victoria	44 74.6%	39 63.9%
B Yamagata	46 78%	36 59%

10. Primary Outcome

Title	Number of Participants With Seroconversion to Influenza Vaccine Antigens: Group 3 (18 to < 65 Years) and Group 4 (>= 65 Years)
Description	Anti-influenza antibodies were measured using the HAI assay for each of the following 4 strains: H1N1, H3N2, B Victoria lineage, and B Yamagata lineage (for Group 3) and for 3 strains: H1N1, H3N2, and B Victoria lineage (for Group 4). Seroconversion was defined as either a pre-vaccination HAI titer < 1:10 and a post-final vaccination titer >= 1:40 or a pre-vaccination titer >= 1:10 and at least a 4-fold increase in post-final vaccination titer.
Time Frame	Day 0 (pre-vaccination) and Day 21 (post-vaccination)

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, "Number analyzed" corresponds to participants with available data for each listed strain and "0" in the number analyzed field signifies that none of the participants were analyzed, since the 2017-2018 formulation of Fluzone High-Dose vaccine did not contain the B Yagamata lineage strain.

Arm/Group Title	Group 3: 18 to < 65 Years	Group 4: >= 65 Years
Arm/Group Description	Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.	Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
Measure Participants	56	59
A/H1N1	26 44.1%	33 54.1%
A/H3N2	22 37.3%	33 54.1%
B Victoria	19 32.2%	18 29.5%
B Yamagata	22 37.3%

Adverse Events

Time Frame	Adverse event (AE) data were collected from Day 0 (post-vaccination) up to Day 56 for Groups 1 and 2; up to Day 21 for Groups 3 and 4.
Adverse Event Reporting Description	A solicited reaction is an AE that is prelisted in the electronic case report form (eCRF) and considered to be related to vaccination. A solicited reaction is therefore an adverse drug reaction (ADR) observed and reported under the conditions (nature and time to onset) prelisted (i.e., solicited) in the eCRF. An unsolicited AE is an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of symptom and/or time to onset post-vaccination.
Arm/Group Title	Group 1: 6 to < 36 Months		Group 2: 3 to < 9 Years		Group 3: 18 to < 65 Years		Group 4: >= 65 Years
Arm/Group Description	Children aged 6 to < 36 months received a 0.25-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0. For participants for whom 2 doses of influenza vaccine were recommended, a second dose was administered on Day 28.		Children 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, a second dose was administered on Day 28.		Adults aged 18 to < 65 years received a 0.5-mL dose of Fluzone Quadrivalent vaccine, intramuscularly, at Day 0.		Adults aged >= 65 years received a 0.5-mL dose of Fluzone High-Dose vaccine, intramuscularly, at Day 0.
All Cause Mortality
	Group 1: 6 to < 36 Months		Group 2: 3 to < 9 Years		Group 3: 18 to < 65 Years		Group 4: >= 65 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/61 (0%)		0/60 (0%)		0/60 (0%)
Serious Adverse Events
	Group 1: 6 to < 36 Months		Group 2: 3 to < 9 Years		Group 3: 18 to < 65 Years		Group 4: >= 65 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/59 (0%)		0/61 (0%)		2/60 (3.3%)		0/60 (0%)
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous	0/59 (0%)	0	0/61 (0%)	0	1/60 (1.7%)	1	0/60 (0%)	0
Psychiatric disorders
Anxiety	0/59 (0%)	0	0/61 (0%)	0	1/60 (1.7%)	1	0/60 (0%)	0
Depression	0/59 (0%)	0	0/61 (0%)	0	1/60 (1.7%)	1	0/60 (0%)	0
Other (Not Including Serious) Adverse Events
	Group 1: 6 to < 36 Months		Group 2: 3 to < 9 Years		Group 3: 18 to < 65 Years		Group 4: >= 65 Years
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	30/59 (50.8%)		30/61 (49.2%)		29/60 (48.3%)		30/60 (50%)
Gastrointestinal disorders
Vomiting	3/59 (5.1%)	3	1/61 (1.6%)	1	0/60 (0%)	0	0/60 (0%)	0
General disorders
Crying	10/59 (16.9%)	11	1/61 (1.6%)	1	0/60 (0%)	0	0/60 (0%)	0
Injection Site Erythema	4/59 (6.8%)	4	9/61 (14.8%)	9	0/60 (0%)	0	3/60 (5%)	3
Injection Site Pain	16/59 (27.1%)	18	26/61 (42.6%)	26	27/60 (45%)	27	20/60 (33.3%)	20
Injection Site Swelling	2/59 (3.4%)	2	11/61 (18%)	11	1/60 (1.7%)	1	2/60 (3.3%)	2
Malaise	0/59 (0%)	0	3/61 (4.9%)	3	5/60 (8.3%)	5	9/60 (15%)	9
Pyrexia	8/59 (13.6%)	9	2/61 (3.3%)	2	0/60 (0%)	0	1/60 (1.7%)	1
Metabolism and nutrition disorders
Decreased Appetite	7/59 (11.9%)	7	1/61 (1.6%)	1	0/60 (0%)	0	0/60 (0%)	0
Musculoskeletal and connective tissue disorders
Myalgia	0/59 (0%)	0	11/61 (18%)	11	13/60 (21.7%)	13	17/60 (28.3%)	17
Nervous system disorders
Headache	1/59 (1.7%)	1	2/61 (3.3%)	2	10/60 (16.7%)	10	7/60 (11.7%)	7
Somnolence	11/59 (18.6%)	13	1/61 (1.6%)	1	0/60 (0%)	0	0/60 (0%)	0
Psychiatric disorders
Irritability	13/59 (22%)	13	1/61 (1.6%)	1	0/60 (0%)	0	0/60 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	4/59 (6.8%)	5	0/61 (0%)	0	0/60 (0%)	0	2/60 (3.3%)	2

Limitations/Caveats

[Not Specified]

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

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject 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.