Trial Outcomes & Findings for Safety and Immunogenicity of High-Dose Quadrivalent Influenza Vaccine in Participants ≥65 Years in the US (NCT NCT03282240)

Last Updated: 2022-04-07

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

2670 participants

Primary outcome timeframe

Day 28 post-vaccination

Results posted on

2022-04-07

Participant Flow

Study participants were screened in 35 centers in the Unites States (US) from 08 September 2017 to 15 September 2017.

A total of 2670 participants were randomized in the study.

Participant milestones

Participant milestones
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 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.	High-Dose Trivalent Influenza Vaccine (Licensed TIV-HD1) 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.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) 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.
Overall Study STARTED	1777	443	450
Overall Study COMPLETED	1767	440	447
Overall Study NOT COMPLETED	10	3	3

Reasons for withdrawal

Reasons for withdrawal
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) 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.	High-Dose Trivalent Influenza Vaccine (Licensed TIV-HD1) 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.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) 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.
Overall Study Adverse Event	2	2	0
Overall Study Lost to Follow-up	3	0	0
Overall Study Protocol Deviation	4	1	2
Overall Study Withdrawal by Subject	1	0	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine (Licensed TIV-HD1) n=443 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	Total n=2670 Participants Total of all reporting groups
Age, Continuous	72.9 years STANDARD_DEVIATION 5.63 • n=93 Participants	72.8 years STANDARD_DEVIATION 5.79 • n=4 Participants	73.2 years STANDARD_DEVIATION 5.49 • n=27 Participants	73.0 years STANDARD_DEVIATION 5.64 • n=483 Participants
Sex: Female, Male Female	1027 Participants n=93 Participants	268 Participants n=4 Participants	252 Participants n=27 Participants	1547 Participants n=483 Participants
Sex: Female, Male Male	750 Participants n=93 Participants	175 Participants n=4 Participants	198 Participants n=27 Participants	1123 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	9 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	14 Participants n=483 Participants
Race (NIH/OMB) Asian	13 Participants n=93 Participants	2 Participants n=4 Participants	3 Participants n=27 Participants	18 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	4 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	6 Participants n=483 Participants
Race (NIH/OMB) Black or African American	123 Participants n=93 Participants	41 Participants n=4 Participants	35 Participants n=27 Participants	199 Participants n=483 Participants
Race (NIH/OMB) White	1618 Participants n=93 Participants	395 Participants n=4 Participants	402 Participants n=27 Participants	2415 Participants n=483 Participants
Race (NIH/OMB) More than one race	6 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	9 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants	1 Participants n=4 Participants	4 Participants n=27 Participants	9 Participants n=483 Participants

PRIMARY outcome

Timeframe: Day 28 post-vaccination

Population: 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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1680 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=423 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=430 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) n=853 Participants 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.
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2	563 titers (1/dilution) Interval 525.0 to 603.0	588 titers (1/dilution) Interval 513.0 to 673.0	600 titers (1/dilution) Interval 524.0 to 687.0	594 titers (1/dilution) Interval 540.0 to 653.0
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria	516 titers (1/dilution) Interval 488.0 to 545.0	476 titers (1/dilution) Interval 426.0 to 532.0	—	—
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata	578 titers (1/dilution) Interval 547.0 to 612.0	—	580 titers (1/dilution) Interval 519.0 to 649.0	—
Geometric Mean Titers (GMTs) of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1	312 titers (1/dilution) Interval 292.0 to 332.0	387 titers (1/dilution) Interval 339.0 to 442.0	362 titers (1/dilution) Interval 317.0 to 413.0	374 titers (1/dilution) Interval 341.0 to 411.0

PRIMARY outcome

Timeframe: Day 28 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1680 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=423 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=430 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) n=853 Participants 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.
Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1	50.4 percentage of participants Interval 48.0 to 52.8	56.2 percentage of participants Interval 51.3 to 61.0	51.2 percentage of participants Interval 46.3 to 56.0	53.7 percentage of participants Interval 50.2 to 57.1
Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2	49.8 percentage of participants Interval 47.3 to 52.2	52.9 percentage of participants Interval 48.0 to 57.7	48.1 percentage of participants Interval 43.3 to 53.0	50.5 percentage of participants Interval 47.1 to 53.9
Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria	36.5 percentage of participants Interval 34.2 to 38.9	39.0 percentage of participants Interval 34.3 to 43.8	—	—
Percentage of Participants Achieving Seroconversion Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata	46.6 percentage of participants Interval 44.2 to 49.0	—	48.4 percentage of participants Interval 43.5 to 53.2	—

SECONDARY outcome

Timeframe: Day 28 post-vaccination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1763 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=439 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=446 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria	515 titers (1/dilution) Interval 488.0 to 543.0	—	253 titers (1/dilution) Interval 227.0 to 283.0	—
GMTs of B Strains Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata	573 titers (1/dilution) Interval 542.0 to 605.0	280 titers (1/dilution) Interval 249.0 to 316.0	—	—

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1680 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=423 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=430 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1: Day28/Day 0	4.38 ratio Interval 4.11 to 4.66	5.57 ratio Interval 4.85 to 6.39	4.76 ratio Interval 4.16 to 5.44	—
GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2: Day28/Day 0	4.65 ratio Interval 4.35 to 4.98	4.82 ratio Interval 4.24 to 5.48	4.94 ratio Interval 4.32 to 5.65	—
GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria: Day28/Day 0	3.17 ratio Interval 2.99 to 3.35	3.35 ratio Interval 2.99 to 3.76	1.65 ratio Interval 1.52 to 1.78	—
GMT Ratios of Influenza Antibodies Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata: Day28/Day 0	3.82 ratio Interval 3.62 to 4.03	1.86 ratio Interval 1.73 to 2.02	3.82 ratio Interval 3.43 to 4.24	—

SECONDARY outcome

Timeframe: Day 28 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1763 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=439 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=446 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
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 B Victoria	36.3 percentage of participants Interval 34.1 to 38.6	—	15.5 percentage of participants Interval 12.3 to 19.3	—
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 B Yamagata	46.7 percentage of participants Interval 44.3 to 49.0	17.4 percentage of participants Interval 14.0 to 21.3	—	—

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1680 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=423 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=430 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1: Day 0	69.4 percentage of participants Interval 67.2 to 71.6	67.9 percentage of participants Interval 63.2 to 72.3	70.1 percentage of participants Interval 65.5 to 74.4	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2: Day 0	77.4 percentage of participants Interval 75.3 to 79.4	78.1 percentage of participants Interval 73.8 to 82.0	77.8 percentage of participants Interval 73.6 to 81.7	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria: Day 0	88.9 percentage of participants Interval 87.2 to 90.3	87.9 percentage of participants Interval 84.4 to 90.8	88.8 percentage of participants Interval 85.4 to 91.6	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata : Day 0	89.6 percentage of participants Interval 88.0 to 91.0	88.1 percentage of participants Interval 84.6 to 91.1	90.9 percentage of participants Interval 87.8 to 93.4	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1: Day 28	95.1 percentage of participants Interval 94.0 to 96.1	96.7 percentage of participants Interval 94.5 to 98.2	95.6 percentage of participants Interval 93.2 to 97.3	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2: Day 28	96.9 percentage of participants Interval 96.0 to 97.7	96.9 percentage of participants Interval 94.8 to 98.4	96.7 percentage of participants Interval 94.6 to 98.2	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria: Day 28	99.0 percentage of participants Interval 98.5 to 99.5	99.1 percentage of participants Interval 97.6 to 99.7	96.5 percentage of participants Interval 94.3 to 98.0	—
Percentage of Participants Achieving Seroprotection Against Antigens Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata : Day 28	99.3 percentage of participants Interval 98.8 to 99.7	96.7 percentage of participants Interval 94.5 to 98.2	99.1 percentage of participants Interval 97.6 to 99.7	—

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccination

Population: 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

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).

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=102 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=102 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=99 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
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 A/H1N1: Day 0	412 titers (1/dilution) Interval 306.0 to 555.0	427 titers (1/dilution) Interval 328.0 to 556.0	416 titers (1/dilution) Interval 311.0 to 555.0	—
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 A/H3N2: Day 0	497 titers (1/dilution) Interval 417.0 to 592.0	536 titers (1/dilution) Interval 436.0 to 660.0	593 titers (1/dilution) Interval 493.0 to 715.0	—
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 B Victoria: Day 0	458 titers (1/dilution) Interval 359.0 to 583.0	452 titers (1/dilution) Interval 367.0 to 556.0	430 titers (1/dilution) Interval 344.0 to 537.0	—
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 B Yamagata: Day 0	156 titers (1/dilution) Interval 124.0 to 196.0	155 titers (1/dilution) Interval 126.0 to 190.0	192 titers (1/dilution) Interval 152.0 to 242.0	—
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 A/H1N1: Day 28	2229 titers (1/dilution) Interval 1789.0 to 2776.0	2050 titers (1/dilution) Interval 1564.0 to 2687.0	1686 titers (1/dilution) Interval 1331.0 to 2135.0	—
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 A/H3N2: Day 28	1404 titers (1/dilution) Interval 1133.0 to 1741.0	1327 titers (1/dilution) Interval 1056.0 to 1667.0	1301 titers (1/dilution) Interval 1070.0 to 1583.0	—
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 B Victoria: Day 28	1288 titers (1/dilution) Interval 1055.0 to 1573.0	1114 titers (1/dilution) Interval 916.0 to 1354.0	590 titers (1/dilution) Interval 476.0 to 730.0	—
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 B Yamagata: Day 28	546 titers (1/dilution) Interval 438.0 to 682.0	259 titers (1/dilution) Interval 207.0 to 325.0	494 titers (1/dilution) Interval 390.0 to 626.0	—

SECONDARY outcome

Timeframe: Day 0 (pre-vaccination) and Day 28 post-vaccination

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=102 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=102 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=99 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H1N1: Day28/Day 0	5.40 ratio Interval 3.9 to 7.48	5.05 ratio Interval 3.86 to 6.6	4.06 ratio Interval 3.17 to 5.18	—
GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine A/H3N2: Day28/Day 0	2.83 ratio Interval 2.31 to 3.46	2.50 ratio Interval 2.04 to 3.06	2.19 ratio Interval 1.8 to 2.67	—
GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Victoria: Day28/Day 0	2.81 ratio Interval 2.21 to 3.58	2.47 ratio Interval 2.04 to 2.99	1.37 ratio Interval 1.16 to 1.62	—
GMTRs of Influenza Antibodies (SN Assay) Following Vaccination With Either a High-Dose Quadrivalent Influenza Vaccine or High-Dose Trivalent Influenza Vaccine B Yamagata: Day28/Day 0	3.51 ratio Interval 2.8 to 4.39	1.66 ratio Interval 1.41 to 1.95	2.58 ratio Interval 2.18 to 3.05	—

SECONDARY outcome

Timeframe: Day 0, Day 28

Population: Analysis was performed on expanded immunogenicity subset.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=102 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=102 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=99 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=20 (1/dil): Day 0	97 Participants	99 Participants	98 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=40 (1/dil): Day 0	95 Participants	96 Participants	91 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=80 (1/dil): Day 0	89 Participants	89 Participants	84 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=20 (1/dil): Day 0	102 Participants	100 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=40 (1/dil): Day 0	102 Participants	100 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=80 (1/dil): Day 0	99 Participants	100 Participants	98 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=20 (1/dil): Day 0	101 Participants	100 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=40 (1/dil): Day 0	97 Participants	99 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=80 (1/dil): Day 0	91 Participants	96 Participants	93 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=20 (1/dil): Day 0	98 Participants	98 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=40 (1/dil): Day 0	91 Participants	93 Participants	87 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=80 (1/dil): Day 0	75 Participants	75 Participants	74 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=20 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=40 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: >=80 (1/dil): Day 28	102 Participants	100 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=20 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=40 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: >=80 (1/dil): Day 28	102 Participants	101 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=20 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=40 (1/dil): Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: >=80 (1/dil): Day 28	102 Participants	102 Participants	97 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=20 (1/dil): Day 28	102 Participants	101 Participants	99 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=40 (1/dil): Day 28	102 Participants	99 Participants	97 Participants	—
Number of Participants With Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: >=80 (1/dil): Day 28	99 Participants	83 Participants	91 Participants	—

SECONDARY outcome

Timeframe: Day 28

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=102 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=100 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=99 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 2-Fold Rise: A/H1N1	74 Participants	71 Participants	64 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 4-Fold Rise: A/H1N1	43 Participants	50 Participants	41 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 2-Fold Rise: A/H3N2	52 Participants	48 Participants	42 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 4-Fold Rise: A/H3N2	27 Participants	24 Participants	23 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 2-Fold Rise: B Victoria	52 Participants	51 Participants	24 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 4-Fold Rise: B Victoria	28 Participants	23 Participants	8 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 2-Fold Rise: B Yamagata	65 Participants	31 Participants	55 Participants	—
Number of Participants With Two-Fold and Four-Fold Increase in Neutralization Antibody Titer at Day 28 Participants With 4-Fold Rise: B Yamagata	36 Participants	11 Participants	29 Participants	—

SECONDARY outcome

Timeframe: Day 0, Day 28

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

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=102 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=102 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=99 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: Titer >= 1:10: Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: Titer >= 1:10: Day 0	100 Participants	100 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 A/H1N1: Titer >= 1:10: Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: Titer >= 1:10: Day 0	102 Participants	100 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 A/H3N2: Titer >= 1:10: Day 28	102 Participants	102 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 B Victoria: Titer >= 1:10: Day 0	102 Participants	100 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: Titer >= 1:10: Day 0	100 Participants	100 Participants	99 Participants	—
Number of Participants With Detectable Neutralization Antibody Titers at Day 0 and Day 28 B Yamagata: Titer >= 1:10: Day 28	102 Participants	102 Participants	99 Participants	—

SECONDARY outcome

Timeframe: Within 7 days after vaccination

Population: 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.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=443 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
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 Injection Site Pain: Grade 3	12 Participants	1 Participants	1 Participants	—
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 Injection Site Swelling: Any	86 Participants	23 Participants	19 Participants	—
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 Injection Site Swelling: Grade 3	5 Participants	0 Participants	1 Participants	—
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 Fever: Any Grade	7 Participants	3 Participants	5 Participants	—
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 Fever: Grade 3	3 Participants	1 Participants	1 Participants	—
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 Headache: Any Grade	254 Participants	63 Participants	58 Participants	—
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 Headache: Grade 3	11 Participants	2 Participants	2 Participants	—
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 Malaise: Any Grade	233 Participants	52 Participants	67 Participants	—
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 Malaise: Grade 3	13 Participants	3 Participants	1 Participants	—
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 Myalgia: Any Grade	402 Participants	80 Participants	88 Participants	—
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 Myalgia: Grade 3	16 Participants	3 Participants	3 Participants	—
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 Shivering: Any Grade	95 Participants	20 Participants	22 Participants	—
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 Shivering: Grade 3	5 Participants	3 Participants	0 Participants	—
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 Injection Site Bruising: Any	23 Participants	6 Participants	4 Participants	—
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 Injection Site Bruising: Grade 3	0 Participants	0 Participants	0 Participants	—
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 Injection Site Erythema: Any	110 Participants	30 Participants	21 Participants	—
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 Injection Site Erythema: Grade 3	11 Participants	1 Participants	1 Participants	—
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 Injection Site Induration: Any	66 Participants	17 Participants	14 Participants	—
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 Injection Site Induration: Grade 3	3 Participants	0 Participants	1 Participants	—
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 Injection Site Pain: Any	731 Participants	172 Participants	152 Participants	—

SECONDARY outcome

Timeframe: Within 30 minutes after vaccination

Population: Analysis was performed on safety analysis set.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=443 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participants With Immediate Adverse Event (AEs)	5 Participants	0 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Within 28 days after vaccination

Population: Analysis was performed on safety analysis set.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=443 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participant With Unsolicited Adverse Event (AE)	292 Participants	79 Participants	68 Participants	—

SECONDARY outcome

Timeframe: Up to 6 months after vaccination

Population: Analysis was performed on safety analysis set.

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.

Outcome measures

Outcome measures
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 Participants Participants randomized to receive a single injection of 0.7 mL QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=443 Participants Participants randomized to receive a single injection of 0.5 mL licensed TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 Participants Participants randomized to receive a single injection of 0.5 mL investigational TIV-HD2 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines Pooled (TIV-HDs Pooled) 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.
Number of Participant With Serious Adverse Event	80 Participants	29 Participants	19 Participants	—

Adverse Events

High-Dose Quadrivalent Influenza Vaccine (QIV-HD)

Serious events: 80 serious events

Other events: 935 other events

Deaths: 3 deaths

High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1)

Serious events: 29 serious events

Other events: 234 other events

Deaths: 2 deaths

High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2)

Serious events: 19 serious events

Other events: 206 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	High-Dose Quadrivalent Influenza Vaccine (QIV-HD) n=1777 participants at risk Participants randomized to receive a single injection of the high dose QIV-HD by IM route at Day 0.	High-Dose Trivalent Influenza Vaccines (Licensed TIV-HD1) n=443 participants at risk Participants randomized to receive a single injection of the licensed high dose TIV-HD1 by IM route at Day 0.	High-Dose Trivalent Influenza Vaccine(Investigational TIV-HD2) n=450 participants at risk Participants randomized to receive a single injection of the investigational TIV-HD2 by IM route at Day 0.
General disorders Chills	5.4% 96/1777 • Number of events 97 • 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). 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.	4.5% 20/443 • Number of events 20 • 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). 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.	4.9% 22/450 • Number of events 22 • 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). 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.
General disorders Injection Site Erythema	6.2% 110/1777 • Number of events 112 • 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). 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.	6.8% 30/443 • Number of events 31 • 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). 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.	4.7% 21/450 • Number of events 21 • 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). 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.
General disorders Injection Site Pain	41.1% 731/1777 • Number of events 731 • 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). 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.	38.8% 172/443 • Number of events 172 • 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). 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.	33.8% 152/450 • Number of events 152 • 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). 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.
General disorders Injection Site Swelling	4.8% 86/1777 • Number of events 87 • 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). 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.	5.2% 23/443 • Number of events 23 • 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). 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.	4.2% 19/450 • Number of events 19 • 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). 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.
General disorders Malaise	13.1% 233/1777 • Number of events 234 • 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). 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.	11.7% 52/443 • Number of events 53 • 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). 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.	14.9% 67/450 • Number of events 67 • 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). 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.
Musculoskeletal and connective tissue disorders Myalgia	22.7% 404/1777 • Number of events 404 • 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). 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.	18.3% 81/443 • Number of events 81 • 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). 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.	19.6% 88/450 • Number of events 88 • 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). 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.
Nervous system disorders Headache	14.5% 258/1777 • Number of events 262 • 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). 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.	14.7% 65/443 • Number of events 65 • 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). 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.	13.1% 59/450 • Number of events 61 • 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). 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.

Additional Information

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