Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Participants ≥65 Years in the US

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03282240
• Collaborator: (none)
• Enrollment: 2,670
• Locations: 36
• Arms: 3
• Actual Duration (Months): 7.3
• Patients Per Site: 74.2
• Patients Per Site Per Month: 10.1

Study Details

Study Description

Brief Summary

This randomized, modified double-blind, active-controlled, multi-center trial assessed the safety and immunogenicity of the high-dose quadrivalent influenza vaccine (QIV-HD) compared to either the licensed or investigational high-dose trivalent influenza vaccine (TIV-HD) in adults.

Condition or Disease	Intervention/Treatment	Phase
Influenza	Biological: QIV-HD; Biological: Licensed TIV-HD1; Biological: Investigational TIV-HD2	Phase 3

Detailed Description

This randomized, modified double-blind, active-controlled, multi-center trial was conducted in healthy adults (greater than and equal to [>=] 65 years) to assess the safety and immunogenicity (geometric mean titers and seroconversion for the 4 virus strains at 28 days post vaccination) of the QIV-HD compared to one of the TIV-HDs containing either the B strain from the primary lineage (TIV-HD1; licensed vaccine [Fluzone® High-Dose] for the 2017-2018 Northern Hemisphere [NH] influenza season) or the B strain from the alternate lineage (TIV-HD2, investigational TIV-HD containing an alternate B strain).

Study Design

• Study Type: Interventional
• Actual Enrollment: 2670 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: QHD00013 was a phase III, randomized, modified double-blind, active-controlled, multi-center trial.QHD00013 was a phase III, randomized, modified double-blind, active-controlled, multi-center trial.
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: QHD00013 was a modified double-blind trial with an unblinded administrator used at each trial site. The administrator was not involved in any of the blinded study assessments (e.g., safety).
• Primary Purpose: Prevention
• Official Title: Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine Administered by Intramuscular Route in Participants Aged 65 Years and Older
• Actual Study Start Date: Sep 8, 2017
• Actual Primary Completion Date: Nov 2, 2017
• Actual Study Completion Date: Apr 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: QIV-HD Participants randomized to receive a single injection of 0.7 mL QIV-HD by intramuscular (IM) route at Day 0.	Biological: QIV-HD; 0.7 mL-dose was administered intramuscularly (IM) into the upper arm area.; Other Names: High-dose quadrivalent influenza vaccine
Active Comparator: TIV-HD1 (Licensed TIV-HD1) Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Biological: Licensed TIV-HD1; 0.5 mL-dose was administered IM into the upper arm area.; Other Names: High-dose trivalent influenza vaccine
Active Comparator: TIV-HD2 (Investigational TIV-HD2) Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Biological: Investigational TIV-HD2; 0.5 mL-dose was administered IM into the upper arm area.; Other Names: High-dose trivalent influenza vaccine (alternate B strain)

Outcome Measures

Primary Outcome Measures

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

   GMTs of anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.

2. Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 28 post-vaccination]

   Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Seroconversion was defined as either a HAI titer less than (<) 10 (1/dilution) at Day 0 and post-injection titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.

Secondary Outcome Measures

1. GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 28 post-vaccination]

   Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). For each B strain, the immunogenicity of QIV-HD was compared to that of TIV-HD group which contains the corresponding B strain. TIV-HD1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.

2. GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]

   GMTs of anti-influenza antibodies using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Geometric Mean Titers Ratios (GMTRs) were calculated as the ratio of GMTs post vaccination and pre-vaccination.

3. Percentage of Participants Achieving Seroconversion Against Antigens of B Strains After Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 28 post-vaccination]

   Seroconversion was defined as either a HAI titer <10 (1/dilution) at Day 0 and post-injection titer >=40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28.

4. Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]

   Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28.

5. Geometric Mean Titers of Influenza Antibodies (Seroneutralization [SN] Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]

   GMTs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2).

6. GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Day 0 (pre-vaccination) and Day 28 post-vaccination]

   GMTRs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.

7. Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 [Day 0, Day 28]

   Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Neutralizing antibody was defined as titers >=20 (1/dilution), >=40 (1/dilution), >=80 (1/dilution) at Day 0 and Day 28.

8. Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 [Day 28]

   Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / baseline computed value.

9. Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 [Day 0, Day 28]

   Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Detectable neutralization antibody titer >= 1:10 (1/dilution) at Day 0 and Day 28.

10. Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine [Within 7 days after vaccination]

    Solicited injection site: Pain, Erythema, Swelling, Induration, and Bruising. Grade 3 reactions: Pain - interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Erythema, Swelling, Induration, and Bruising: >100 millimeters (mm). Systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Shivering: interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.

11. Number of Participants With Immediate Adverse Event (AEs) [Within 30 minutes after vaccination]

    Participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurring during that time was recorded as immediate unsolicited systemic AEs (AEs that were related to the investigational product) in the case report book (CRB). Unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/ or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.

12. Number of Participant With Unsolicited Adverse Event (AE) [Within 28 days after vaccination]

    An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.

13. Number of Participant With Serious Adverse Event [Up to 6 months after vaccination]

    An serious adverse event was any untoward medical occurrence that at any dose results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect, or was an important medical event.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Aged >= 65 years on the day of inclusion.

• Informed consent form had been signed and dated.

• Able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

• Participation at the time of trial enrollment (or in the 4 weeks preceding the 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 4 weeks (28 days) preceding the trial vaccination or planned receipt of any vaccine prior to Visit 2.

• Previous vaccination against influenza (in the preceding 6 months) 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 vaccines used in the trial or to a vaccine containing any of the same substances.

• Thrombocytopenia or bleeding disorder, contraindicating IM vaccination based on investigator's judgment.

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

• Alcohol or substance abuse that, in the opinion of the investigator, might interfere with the trial conduct or completion.

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

• Identified as an Investigator or employee of the Investigator or trial center with direct involvement in the proposed trial, 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 trial.

• Personal or family history of Guillain-Barré syndrome.

• Neoplastic disease or any hematologic malignancy (except localized skin or prostate cancer that is stable at the time of vaccination in the absence of therapy and participants who have a history of neoplastic disease and have been disease free for

= 5 years).

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi Pasteur Investigational Site 037	Anaheim	California	United States	92801
2	Sanofi Pasteur Investigational Site 029	Redding	California	United States	96001
3	Sanofi Pasteur Investigational Site 003	San Diego	California	United States	92117
4	Sanofi Pasteur Investigational Site 016	Colorado Springs	Colorado	United States	80920
5	Sanofi Pasteur Investigational Site 035	Milford	Connecticut	United States	06460
6	Sanofi Pasteur Investigational Site 031	Hollywood	Florida	United States	33024
7	Sanofi Pasteur Investigational Site 009	Jacksonville	Florida	United States	32205
8	Sanofi Pasteur Investigational Site 017	Jacksonville	Florida	United States	32216
9	Sanofi Pasteur Investigational Site 030	Stockbridge	Georgia	United States	30281
10	Sanofi Pasteur Investigational Site 010	Boise	Idaho	United States	83712
11	Sanofi Pasteur Investigational Site 034	Meridian	Idaho	United States	83642
12	Sanofi Pasteur Investigational Site 021	Council Bluffs	Iowa	United States	51501
13	Sanofi Pasteur Investigational Site 023	Wichita	Kansas	United States	67205
14	Sanofi Pasteur Investigational Site 028	Wichita	Kansas	United States	67207
15	Sanofi Pasteur Investigational Site 012	Bardstown	Kentucky	United States	40004
16	Sanofi Pasteur Investigational Site 018	Metairie	Louisiana	United States	70427
17	Sanofi Pasteur Investigational Site 026	Biloxi	Mississippi	United States	39531
18	Sanofi Pasteur Investigational Site 014	Saint Louis	Missouri	United States	63104
19	Sanofi Pasteur Investigational Site 011	Omaha	Nebraska	United States	68134
20	Sanofi Pasteur Investigational Site 024	Las Vegas	Nevada	United States	89104
21	Sanofi Pasteur Investigational Site 008	Rochester	New York	United States	14609
22	Sanofi Pasteur Investigational Site 005	Wilmington	North Carolina	United States	28401
23	Sanofi Pasteur Investigational Site 036	Winston-Salem	North Carolina	United States	27045
24	Sanofi Pasteur Investigational Site 004	Cleveland	Ohio	United States	44122
25	Sanofi Pasteur Investigational Site 015	Oklahoma City	Oklahoma	United States	73112
26	Sanofi Pasteur Investigational Site 013	Warwick	Rhode Island	United States	02886
27	Sanofi Pasteur Investigational Site 033	Mount Pleasant	South Carolina	United States	29464
28	Sanofi Pasteur Investigational Site 001	Nashville	Tennessee	United States	37212
29	Sanofi Pasteur Investigational Site 002	Dallas	Texas	United States	75234
30	Sanofi Pasteur Investigational Site 025	Tomball	Texas	United States	77375
31	Sanofi Pasteur Investigational Site 027	Salt Lake City	Utah	United States	84109
32	Sanofi Pasteur Investigational Site 006	Salt Lake City	Utah	United States	84121
33	Sanofi Pasteur Investigational Site 019	Salt Lake City	Utah	United States	84123
34	Sanofi Pasteur Investigational Site 020	South Jordan	Utah	United States	84095
35	Sanofi Pasteur Investigational Site 022	West Jordan	Utah	United States	83642
36	Sanofi Pasteur Investigational Site 038	Norfolk	Virginia	United States	23507

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

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

Study Documents (Full-Text)

• Study Protocol - Jul 20, 2017
• Statistical Analysis Plan - Apr 18, 2018

More Information

Additional Information:

• Related info
• Related info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT03282240
• Other Study ID Numbers: QHD00013; U1111-1183-5556
• First Posted: Sep 13, 2017
• Last Update Posted: Apr 7, 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
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were screened in 35 centers in the Unites States (US) from 08 September 2017 to 15 September 2017.
Pre-assignment Detail	A total of 2670 participants were randomized in the study.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccine (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL high dose quadrivalent influenza vaccine (QIV-HD) by intramuscular (IM) route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed high dose trivalent influenza vaccine (TIV-HD1) by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational high dose trivalent influenza vaccine with alternate B strain (TIV-HD2) by IM route at Day 0.
Period Title: Overall Study
STARTED	1777	443	450
COMPLETED	1767	440	447
NOT COMPLETED	10	3	3

Baseline Characteristics

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccine (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)	Total
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Total of all reporting groups
Overall Participants	1777	443	450	2670
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	72.9 (5.63)	72.8 (5.79)	73.2 (5.49)	73.0 (5.64)
Sex: Female, Male (Count of Participants)
Female	1027 57.8%	268 60.5%	252 56%	1547 57.9%
Male	750 42.2%	175 39.5%	198 44%	1123 42.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	9 0.5%	2 0.5%	3 0.7%	14 0.5%
Asian	13 0.7%	2 0.5%	3 0.7%	18 0.7%
Native Hawaiian or Other Pacific Islander	4 0.2%	1 0.2%	1 0.2%	6 0.2%
Black or African American	123 6.9%	41 9.3%	35 7.8%	199 7.5%
White	1618 91.1%	395 89.2%	402 89.3%	2415 90.4%
More than one race	6 0.3%	1 0.2%	2 0.4%	9 0.3%
Unknown or Not Reported	4 0.2%	1 0.2%	4 0.9%	9 0.3%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	GMTs of anti-influenza antibodies were measured using an hemagglutination inhibition (HAI) assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Per-protocol analysis set (PPAS): all randomized participants who received at least 1 dose of trial vaccine & had a post-vaccination blood sample HAI result for at least 1 strain, with no relevant protocol deviations. Here, 'number analyzed' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Participants randomized to receive either a single injection of 0.5 mL licensed TIV-HD1 or investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1680	423	430	853
A/H1N1	312	387	362	374
A/H3N2	563	588	600	594
B Victoria	516	476
B Yamagata	578	580

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)
	Comments	B Victoria: The 2-sided 95% confidence interval (CI) was based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of GMTs was concluded if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups is > 0.667 for each of the comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; 0.958 to 1.224
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Comments	B Yamagata: The 2-sided 95% CI was based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of GMTs was concluded if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups is > 0.667 for each of the comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	1.00
	Confidence Interval	(2-Sided) 95%; 0.881 to 1.129
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
	Comments	A/H1N1: The 2-sided 95% CI was based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of GMTs was concluded if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups is > 0.667 for each of the comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	0.83
	Confidence Interval	(2-Sided) 95%; 0.744 to 0.932
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
	Comments	A/H3N2: The 2-sided 95% CI was based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority of GMTs was concluded if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups is > 0.667 for each of the comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	0.95
	Confidence Interval	(2-Sided) 95%; 0.842 to 1.066
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	Anti-influenza antibodies were measured using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Seroconversion was defined as either a HAI titer less than (<) 10 (1/dilution) at Day 0 and post-injection titer greater than or equal to (>=) 40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28. For each A strain, the comparison was made with the pooled TIV-HD groups. For each B strain, the comparison was made with the TIV-HD group containing the corresponding B strain. TIV-HD 1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPAS. Here, 'number analyzed' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Participants randomized to receive either a single injection of 0.5 mL licensed TIV-HD1 or investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1680	423	430	853
A/H1N1	50.4 2.8%	56.2 12.7%	51.2 11.4%	53.7 2%
A/H3N2	49.8 2.8%	52.9 11.9%	48.1 10.7%	50.5 1.9%
B Victoria	36.5 2.1%	39.0 8.8%
B Yamagata	46.6 2.6%	48.4 10.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)
	Comments	B Victoria: The 2-sided 95% CI for the difference is based on the Wilson score method without continuity correction.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority in seroconversion was concluded if the lower limit of the 2-sided 95% CI of the differences of seroconversion rates between groups is > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-2.41
	Confidence Interval	(2-Sided) 95%; -7.66 to 2.70
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Comments	B Yamagata: The 2-sided 95% CI for the difference is based on the Wilson score method without continuity correction.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority in seroconversion was concluded if the lower limit of the 2-sided 95% CI of the differences of seroconversion rates between groups is > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-1.75
	Confidence Interval	(2-Sided) 95%; -7.04 to 3.53
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
	Comments	A/H3N2: The 2-sided 95% CI for the difference is based on the Wilson score method without continuity correction.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority in seroconversion was concluded if the lower limit of the 2-sided 95% CI of the differences of seroconversion rates between groups is > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-0.71
	Confidence Interval	(2-Sided) 95%; -4.83 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled)
	Comments	A/H1N1: The 2-sided 95% CI for the difference is based on the Wilson score method without continuity correction.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority in seroconversion was concluded if the lower limit of the 2-sided 95% CI of the differences of seroconversion rates between groups is > -10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-3.27
	Confidence Interval	(2-Sided) 95%; -7.37 to 0.86
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). For each B strain, the immunogenicity of QIV-HD was compared to that of TIV-HD group which contains the corresponding B strain. TIV-HD1 did not contain B2 strain; TIV-HD2 did not contain B1 strain.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on full analysis set (FAS) that consisted who received at least 1 dose of a trial vaccine and had a post-vaccination blood sample HAI result for at least 1 strain. Participants were analyzed according to the vaccine group to which they were randomized.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1763	439	446
B Victoria	515	253
B Yamagata	573	280

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)
	Comments	The 2-sided 95% CI is based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Superiority
	Comments	Superiority in GMTs was observed if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups was > 1.5 for comparison group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	2.04
	Confidence Interval	(2-Sided) 95%; 1.804 to 2.315
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Comments	The 2-sided 95% CI is based on the Student t-distribution of logarithmic transformation of the individual titers. Antilog transformations were applied to the results.
	Type of Statistical Test	Superiority
	Comments	Superiority in GMTs was observed if the lower limit of the 2-sided 95% CI of the ratio of GMTs between groups was > 1.5 for comparison group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMT Ratio (QIV-HD/TIV-HDs)
	Estimated Value	2.03
	Confidence Interval	(2-Sided) 95%; 1.802 to 2.288
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	GMTs of anti-influenza antibodies using an HAI assay for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Geometric Mean Titers Ratios (GMTRs) were calculated as the ratio of GMTs post vaccination and pre-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' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational high dose trivalent influenza vaccine with alternate B strain (TIV-HD2) by IM route at Day 0.
Measure Participants	1680	423	430
A/H1N1: Day28/Day 0	4.38	5.57	4.76
A/H3N2: Day28/Day 0	4.65	4.82	4.94
B Victoria: Day28/Day 0	3.17	3.35	1.65
B Yamagata: Day28/Day 0	3.82	1.86	3.82

5. Secondary Outcome

Title	Percentage of Participants Achieving Seroconversion Against Antigens of B Strains After Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	Seroconversion was defined as either a HAI titer <10 (1/dilution) at Day 0 and post-injection titer >=40 (1/dilution) at Day 28, or HAI titer >=10 (1/dilution) at Day 0 and a >=4-fold increase in HAI titer (1/dilution) at Day 28.
Time Frame	Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on FAS. Here, 'number analyzed' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1763	439	446
B Victoria	36.3 2%	15.5 3.5%
B Yamagata	46.7 2.6%	17.4 3.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)
	Comments	B Yamagata: The 2-sided 95% CI for the difference was based on the Wilson score method without continuity correction.
	Type of Statistical Test	Superiority
	Comments	Superiority in seroconversion was observed if the lower limit of the 2-sided 95% CI of the difference of seroconversion rates between groups is > 10% for each applicable comparison.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	29.27
	Confidence Interval	(2-Sided) 95%; 24.78 to 33.29
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High-Dose Quadrivalent Influenza Vaccine (QIV-HD), High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Comments	B Victoria: The 2-sided 95% CI for the difference was based on the Wilson score method without continuity correction.
	Type of Statistical Test	Superiority
	Comments	Superiority in seroconversion was observed if the lower limit of the 2-sided 95% CI of the difference of seroconversion rates between groups is > 10% for each applicable comparison.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	20.78
	Confidence Interval	(2-Sided) 95%; 16.5 to 24.61
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	Anti-influenza antibodies were measured using HAI assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). Seroprotection was defined as a HAI titer >=40 (1/dilution) at Day 0 and Day 28.
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' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1680	423	430
A/H1N1: Day 0	69.4 3.9%	67.9 15.3%	70.1 15.6%
A/H3N2: Day 0	77.4 4.4%	78.1 17.6%	77.8 17.3%
B Victoria: Day 0	88.9 5%	87.9 19.8%	88.8 19.7%
B Yamagata : Day 0	89.6 5%	88.1 19.9%	90.9 20.2%
A/H1N1: Day 28	95.1 5.4%	96.7 21.8%	95.6 21.2%
A/H3N2: Day 28	96.9 5.5%	96.9 21.9%	96.7 21.5%
B Victoria: Day 28	99.0 5.6%	99.1 22.4%	96.5 21.4%
B Yamagata : Day 28	99.3 5.6%	96.7 21.8%	99.1 22%

7. Secondary Outcome

Title	Geometric Mean Titers of Influenza Antibodies (Seroneutralization [SN] Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	GMTs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2).
Time Frame	Day 0 (pre-vaccination) and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Expanded immunogenicity subset:participants who received at least 1 dose of trial vaccine& had post-vaccination blood sample HAI result for at least 1 strain& were randomized into expanded immunogenicity subset with at least 1 post-vaccination SN assay result for at least 1 strain.'Number analyzed'=participants with available data for each category

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	102	102	99
A/H1N1: Day 0	412	427	416
A/H3N2: Day 0	497	536	593
B Victoria: Day 0	458	452	430
B Yamagata: Day 0	156	155	192
A/H1N1: Day 28	2229	2050	1686
A/H3N2: Day 28	1404	1327	1301
B Victoria: Day 28	1288	1114	590
B Yamagata: Day 28	546	259	494

8. Secondary Outcome

Title	GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	GMTRs of anti-influenza antibodies were measured using SN assay for 4 strains: A/H1N1 (A1), A/H3N2 (A2), B Victoria lineage (B1), and B Yamagata lineage (B2). GMTRs were calculated as the ratio of GMTs post vaccination and pre-vaccination.
Time Frame	Day 0 (pre-vaccination) and Day 28 post-vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on expanded immunogenicity subset. Here, 'number analyzed' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	102	102	99
A/H1N1: Day28/Day 0	5.40	5.05	4.06
A/H3N2: Day28/Day 0	2.83	2.50	2.19
B Victoria: Day28/Day 0	2.81	2.47	1.37
B Yamagata: Day28/Day 0	3.51	1.66	2.58

9. Secondary Outcome

Title	Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28
Description	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Neutralizing antibody was defined as titers >=20 (1/dilution), >=40 (1/dilution), >=80 (1/dilution) at Day 0 and Day 28.
Time Frame	Day 0, Day 28

Outcome Measure Data

Analysis Population Description

Analysis was performed on expanded immunogenicity subset.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of the high dose QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	102	102	99
A/H1N1: >=20 (1/dil): Day 0	97 5.5%	99 22.3%	98 21.8%
A/H1N1: >=40 (1/dil): Day 0	95 5.3%	96 21.7%	91 20.2%
A/H1N1: >=80 (1/dil): Day 0	89 5%	89 20.1%	84 18.7%
A/H3N2: >=20 (1/dil): Day 0	102 5.7%	100 22.6%	99 22%
A/H3N2: >=40 (1/dil): Day 0	102 5.7%	100 22.6%	99 22%
A/H3N2: >=80 (1/dil): Day 0	99 5.6%	100 22.6%	98 21.8%
B Victoria: >=20 (1/dil): Day 0	101 5.7%	100 22.6%	99 22%
B Victoria: >=40 (1/dil): Day 0	97 5.5%	99 22.3%	99 22%
B Victoria: >=80 (1/dil): Day 0	91 5.1%	96 21.7%	93 20.7%
B Yamagata: >=20 (1/dil): Day 0	98 5.5%	98 22.1%	99 22%
B Yamagata: >=40 (1/dil): Day 0	91 5.1%	93 21%	87 19.3%
B Yamagata: >=80 (1/dil): Day 0	75 4.2%	75 16.9%	74 16.4%
A/H1N1: >=20 (1/dil): Day 28	102 5.7%	102 23%	99 22%
A/H1N1: >=40 (1/dil): Day 28	102 5.7%	102 23%	99 22%
A/H1N1: >=80 (1/dil): Day 28	102 5.7%	100 22.6%	99 22%
A/H3N2: >=20 (1/dil): Day 28	102 5.7%	102 23%	99 22%
A/H3N2: >=40 (1/dil): Day 28	102 5.7%	102 23%	99 22%
A/H3N2: >=80 (1/dil): Day 28	102 5.7%	101 22.8%	99 22%
B Victoria: >=20 (1/dil): Day 28	102 5.7%	102 23%	99 22%
B Victoria: >=40 (1/dil): Day 28	102 5.7%	102 23%	99 22%
B Victoria: >=80 (1/dil): Day 28	102 5.7%	102 23%	97 21.6%
B Yamagata: >=20 (1/dil): Day 28	102 5.7%	101 22.8%	99 22%
B Yamagata: >=40 (1/dil): Day 28	102 5.7%	99 22.3%	97 21.6%
B Yamagata: >=80 (1/dil): Day 28	99 5.6%	83 18.7%	91 20.2%

10. Secondary Outcome

Title	Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28
Description	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). 2-fold and 4-fold rise was defined as the computed value = post-vaccination computed value / baseline computed value.
Time Frame	Day 28

Outcome Measure Data

Analysis Population Description

Analysis was performed on expanded immunogenicity subset. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of the high dose QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational high dose trivalent influenza vaccine with alternate B strain (TIV-HD2) by IM route at Day 0.
Measure Participants	102	100	99
Participants With 2-Fold Rise: A/H1N1	74 4.2%	71 16%	64 14.2%
Participants With 4-Fold Rise: A/H1N1	43 2.4%	50 11.3%	41 9.1%
Participants With 2-Fold Rise: A/H3N2	52 2.9%	48 10.8%	42 9.3%
Participants With 4-Fold Rise: A/H3N2	27 1.5%	24 5.4%	23 5.1%
Participants With 2-Fold Rise: B Victoria	52 2.9%	51 11.5%	24 5.3%
Participants With 4-Fold Rise: B Victoria	28 1.6%	23 5.2%	8 1.8%
Participants With 2-Fold Rise: B Yamagata	65 3.7%	31 7%	55 12.2%
Participants With 4-Fold Rise: B Yamagata	36 2%	11 2.5%	29 6.4%

11. Secondary Outcome

Title	Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28
Description	Neutralizing Antibody titer was measured for each influenza strain with the SN method for 4 strains: A/H1N1, A/H3N2, B Victoria lineage (B1), and B Yamagata lineage (B2). Detectable neutralization antibody titer >= 1:10 (1/dilution) at Day 0 and Day 28.
Time Frame	Day 0, Day 28

Outcome Measure Data

Analysis Population Description

Analysis was performed on expanded immunogenicity subset. Here, 'number analyzed' = participants with available data for each category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of the high dose QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	102	102	99
A/H1N1: Titer >= 1:10: Day 0	100 5.6%	100 22.6%	99 22%
A/H1N1: Titer >= 1:10: Day 28	102 5.7%	102 23%	99 22%
A/H3N2: Titer >= 1:10: Day 0	102 5.7%	100 22.6%	99 22%
A/H3N2: Titer >= 1:10: Day 28	102 5.7%	102 23%	99 22%
B Victoria: Titer >= 1:10: Day 0	102 5.7%	100 22.6%	99 22%
B Victoria: Titer >= 1:10: Day 28	102 5.7%	102 23%	99 22%
B Yamagata: Titer >= 1:10: Day 0	100 5.6%	100 22.6%	99 22%
B Yamagata: Titer >= 1:10: Day 28	102 5.7%	102 23%	99 22%

12. Secondary Outcome

Title	Number of Participants Reporting Solicited Injection-site and Systemic Reactions Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine
Description	Solicited injection site: Pain, Erythema, Swelling, Induration, and Bruising. Grade 3 reactions: Pain - interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention; Erythema, Swelling, Induration, and Bruising: >100 millimeters (mm). Systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 reactions: Fever: >=39°C; Headache, Malaise, Myalgia, and Shivering: interrupts usual activities of daily living, or significantly affects clinical status, or may require intensive therapeutic intervention.
Time Frame	Within 7 days after vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety analysis set that included all participants who had received study vaccine. All participants had their safety analyzed according to the vaccine they actually received. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1777	443	450
Fever: Any Grade	7 0.4%	3 0.7%	5 1.1%
Fever: Grade 3	3 0.2%	1 0.2%	1 0.2%
Headache: Any Grade	254 14.3%	63 14.2%	58 12.9%
Headache: Grade 3	11 0.6%	2 0.5%	2 0.4%
Malaise: Any Grade	233 13.1%	52 11.7%	67 14.9%
Malaise: Grade 3	13 0.7%	3 0.7%	1 0.2%
Myalgia: Any Grade	402 22.6%	80 18.1%	88 19.6%
Myalgia: Grade 3	16 0.9%	3 0.7%	3 0.7%
Shivering: Any Grade	95 5.3%	20 4.5%	22 4.9%
Shivering: Grade 3	5 0.3%	3 0.7%	0 0%
Injection Site Bruising: Any	23 1.3%	6 1.4%	4 0.9%
Injection Site Bruising: Grade 3	0 0%	0 0%	0 0%
Injection Site Erythema: Any	110 6.2%	30 6.8%	21 4.7%
Injection Site Erythema: Grade 3	11 0.6%	1 0.2%	1 0.2%
Injection Site Induration: Any	66 3.7%	17 3.8%	14 3.1%
Injection Site Induration: Grade 3	3 0.2%	0 0%	1 0.2%
Injection Site Pain: Any	731 41.1%	172 38.8%	152 33.8%
Injection Site Pain: Grade 3	12 0.7%	1 0.2%	1 0.2%
Injection Site Swelling: Any	86 4.8%	23 5.2%	19 4.2%
Injection Site Swelling: Grade 3	5 0.3%	0 0%	1 0.2%

13. Secondary Outcome

Title	Number of Participants With Immediate Adverse Event (AEs)
Description	Participants were observed for 30 minutes after vaccination, and any unsolicited systemic AEs occurring during that time was recorded as immediate unsolicited systemic AEs (AEs that were related to the investigational product) in the case report book (CRB). Unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/ or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.
Time Frame	Within 30 minutes after vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety analysis set.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1777	443	450
Count of Participants [Participants]	5 0.3%	0 0%	2 0.4%

14. Secondary Outcome

Title	Number of Participant With Unsolicited Adverse Event (AE)
Description	An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the CRB in terms of symptom and/or onset post-vaccination. Unsolicited AEs included both serious and non-serious unsolicited AEs. A serious adverse event was any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event.
Time Frame	Within 28 days after vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety analysis set.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1777	443	450
Count of Participants [Participants]	292 16.4%	79 17.8%	68 15.1%

15. Secondary Outcome

Title	Number of Participant With Serious Adverse Event
Description	An serious adverse event was any untoward medical occurrence that at any dose results in death, was life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity,is a congenital anomaly/birth defect, or was an important medical event.
Time Frame	Up to 6 months after vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety analysis set.

Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.
Measure Participants	1777	443	450
Count of Participants [Participants]	80 4.5%	29 6.5%	19 4.2%

Adverse Events

Time Frame	Adverse events 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 each vaccination. Serious adverse event data were collected throughout the study (up to 180 days after last vaccination).
Adverse Event Reporting Description	Analysis was performed on safety analysis set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) 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 eCRF in terms of symptom and/or onset post-vaccination.
Arm/Group Title	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)		High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
Arm/Group Description	Participants randomized to receive a single injection of the high dose QIV-HD by IM route at Day 0.		Participants randomized to receive a single injection of the licensed high dose TIV-HD1 by IM route at Day 0.		Participants randomized to receive a single injection of the investigational TIV-HD2 by IM route at Day 0.
All Cause Mortality
	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)		High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/1777 (0.2%)		2/443 (0.5%)		0/450 (0%)
Serious Adverse Events
	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)		High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/1777 (4.5%)		29/443 (6.5%)		19/450 (4.2%)
Blood and lymphatic system disorders
Haemorrhagic Anaemia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Cardiac disorders
Acute Myocardial Infarction	3/1777 (0.2%)	3	0/443 (0%)	0	0/450 (0%)	0
Angina Pectoris	2/1777 (0.1%)	2	0/443 (0%)	0	1/450 (0.2%)	1
Atrial Fibrillation	2/1777 (0.1%)	2	0/443 (0%)	0	1/450 (0.2%)	1
Atrioventricular Block Complete	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Cardiac Failure Congestive	2/1777 (0.1%)	2	1/443 (0.2%)	1	1/450 (0.2%)	2
Coronary Artery Disease	2/1777 (0.1%)	2	3/443 (0.7%)	3	0/450 (0%)	0
Myocardial Infarction	2/1777 (0.1%)	2	1/443 (0.2%)	1	1/450 (0.2%)	1
Pericarditis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Sinus Bradycardia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Stress Cardiomyopathy	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Ventricular Tachycardia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Gastrointestinal disorders
Colitis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Constipation	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Diverticulum Intestinal Haemorrhagic	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Gastritis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Gastrointestinal Haemorrhage	0/1777 (0%)	0	1/443 (0.2%)	2	0/450 (0%)	0
Gastrointestinal Ulcer Haemorrhage	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Inguinal Hernia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Pancreatitis	3/1777 (0.2%)	3	0/443 (0%)	0	0/450 (0%)	0
Small Intestinal Obstruction	2/1777 (0.1%)	2	1/443 (0.2%)	1	0/450 (0%)	0
General disorders
Non-Cardiac Chest Pain	1/1777 (0.1%)	1	1/443 (0.2%)	1	0/450 (0%)	0
Pyrexia	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Sudden Death	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Vascular Stent Thrombosis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Hepatobiliary disorders
Cholangitis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Cholecystitis	1/1777 (0.1%)	1	1/443 (0.2%)	1	0/450 (0%)	0
Cholecystitis Acute	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Cholelithiasis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Infections and infestations
Bacteraemia	2/1777 (0.1%)	2	0/443 (0%)	0	0/450 (0%)	0
Bronchitis	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Diverticulitis	2/1777 (0.1%)	2	0/443 (0%)	0	0/450 (0%)	0
Endocarditis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Influenza	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Parainfluenzae Viral Laryngotracheobronchitis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Pneumonia	6/1777 (0.3%)	7	2/443 (0.5%)	3	0/450 (0%)	0
Respiratory Tract Infection	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Septic Shock	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Staphylococcal Infection	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Streptococcal Infection	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Urinary Tract Infection	2/1777 (0.1%)	2	0/443 (0%)	0	0/450 (0%)	0
Viral Infection	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Injury, poisoning and procedural complications
Anaesthetic Complication	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Ankle Fracture	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Bone Contusion	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Femur Fracture	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Incisional Hernia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Postpericardiotomy Syndrome	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Rib Fracture	0/1777 (0%)	0	1/443 (0.2%)	1	1/450 (0.2%)	1
Road Traffic Accident	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Spinal Compression Fracture	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Tendon Rupture	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Investigations
Troponin Increased	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Metabolism and nutrition disorders
Type 2 Diabetes Mellitus	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Musculoskeletal and connective tissue disorders
Back Pain	2/1777 (0.1%)	2	0/443 (0%)	0	0/450 (0%)	0
Groin Pain	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Intervertebral Disc Protrusion	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Lumbar Spinal Stenosis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Osteoarthritis	6/1777 (0.3%)	6	4/443 (0.9%)	4	0/450 (0%)	0
Pain In Extremity	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Rotator Cuff Syndrome	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Spinal Osteoarthritis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder Cancer	1/1777 (0.1%)	1	1/443 (0.2%)	1	0/450 (0%)	0
Brain Neoplasm	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Breast Cancer	1/1777 (0.1%)	1	0/443 (0%)	0	1/450 (0.2%)	1
Cholangiocarcinoma	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Invasive Ductal Breast Carcinoma	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Malignant Melanoma	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Neoplasm Malignant	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Pancreatic Carcinoma	0/1777 (0%)	0	1/443 (0.2%)	2	0/450 (0%)	0
Prostate Cancer	2/1777 (0.1%)	2	1/443 (0.2%)	1	0/450 (0%)	0
Uterine Leiomyoma	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Nervous system disorders
Carotid Artery Occlusion	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Carotid Artery Stenosis	2/1777 (0.1%)	2	0/443 (0%)	0	0/450 (0%)	0
Cerebrospinal Fluid Leakage	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Cerebrovascular Accident	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Facial Paralysis	1/1777 (0.1%)	1	0/443 (0%)	0	2/450 (0.4%)	2
Ischaemic Cerebral Infarction	0/1777 (0%)	0	1/443 (0.2%)	1	0/450 (0%)	0
Seizure	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Small Fibre Neuropathy	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Syncope	3/1777 (0.2%)	3	0/443 (0%)	0	2/450 (0.4%)	2
Transient Ischaemic Attack	3/1777 (0.2%)	3	0/443 (0%)	0	0/450 (0%)	0
Psychiatric disorders
Mental Status Changes	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Nephropathy	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Urinary Retention	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Reproductive system and breast disorders
Benign Prostatic Hyperplasia	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic Obstructive Pulmonary Disease	1/1777 (0.1%)	1	1/443 (0.2%)	1	0/450 (0%)	0
Dyspnoea	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Pulmonary Embolism	4/1777 (0.2%)	4	0/443 (0%)	0	0/450 (0%)	0
Respiratory Failure	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Skin and subcutaneous tissue disorders
Skin Ulcer	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Vascular disorders
Aortic Stenosis	2/1777 (0.1%)	2	1/443 (0.2%)	1	0/450 (0%)	0
Deep Vein Thrombosis	0/1777 (0%)	0	0/443 (0%)	0	1/450 (0.2%)	1
Peripheral Vascular Disorder	1/1777 (0.1%)	1	0/443 (0%)	0	0/450 (0%)	0
Other (Not Including Serious) Adverse Events
	High-Dose Quadrivalent Influenza Vaccine (QIV-HD)		High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)		High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	935/1777 (52.6%)		234/443 (52.8%)		206/450 (45.8%)
General disorders
Chills	96/1777 (5.4%)	97	20/443 (4.5%)	20	22/450 (4.9%)	22
Injection Site Erythema	110/1777 (6.2%)	112	30/443 (6.8%)	31	21/450 (4.7%)	21
Injection Site Pain	731/1777 (41.1%)	731	172/443 (38.8%)	172	152/450 (33.8%)	152
Injection Site Swelling	86/1777 (4.8%)	87	23/443 (5.2%)	23	19/450 (4.2%)	19
Malaise	233/1777 (13.1%)	234	52/443 (11.7%)	53	67/450 (14.9%)	67
Musculoskeletal and connective tissue disorders
Myalgia	404/1777 (22.7%)	404	81/443 (18.3%)	81	88/450 (19.6%)	88
Nervous system disorders
Headache	258/1777 (14.5%)	262	65/443 (14.7%)	65	59/450 (13.1%)	61

Limitations/Caveats

[Not Specified]

More Information

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 partcipant 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.