FLUAD® vs. Fluzone® High-Dose Study

• ClinicalTrials.gov Identifier: NCT03183908
• Recruitment Status: Completed
• First Posted: June 12, 2017
• Results First Posted: March 30, 2021
• Last Update Posted: March 30, 2021
• Sponsor: Duke University
• Collaborators: Centers for Disease Control and Prevention; Boston Medical Center; Children's Hospital Medical Center, Cincinnati
• Information provided by (Responsible Party): Duke University

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Conditions: Pain; Quality of Life; Injection Site Reaction; Side Effect of Drug; Adverse Drug Event
• Interventions: Biological: FLUAD®; Biological: Fluzone® High-Dose
• Enrollment: 757

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Period Title: Overall Study
Started [1]	378	379
Completed [2]	378	377
Not Completed	0	2
Reason Not Completed
Missing Symptom Diary Data	0	2
[1] Full Analysis Population 2; [2] Full Analysis Population 1

Baseline Characteristics

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD)	High-dose Influenza Vaccine (Fluzone HD)	Total
Arm/Group Description		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	Total of all reporting groups
Overall Number of Baseline Participants		378	379	757
Baseline Analysis Population Description		The primary analysis population will be the Full Analysis Population 2; defined as all subjects who are randomized and vaccinated.
Age, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Age Group	Number Analyzed	378 participants	379 participants	757 participants
	65-79 Years	298 78.8%	296 78.1%	594 78.5%
	80 or More	80 21.2%	83 21.9%	163 21.5%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	378 participants	379 participants	757 participants
	Female	213 56.3%	207 54.6%	420 55.5%
	Male	165 43.7%	172 45.4%	337 44.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	378 participants	379 participants	757 participants
	Hispanic or Latino	7 1.9%	1 0.3%	8 1.1%
	Not Hispanic or Latino	346 91.5%	351 92.6%	697 92.1%
	Unknown or Not Reported	25 6.6%	27 7.1%	52 6.9%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
Race	Number Analyzed	378 participants	379 participants	757 participants
	Black only	70 18.5%	59 15.6%	129 17.0%
	Other	22 5.8%	17 4.5%	39 5.2%
	White Only	286 75.7%	303 79.9%	589 77.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	378 participants	379 participants	757 participants
		378	379	757

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Injection-Site Pain in Arm That Was Vaccinated, Population 1
Description	Comparison of the proportion of subjects reporting moderate/severe injection site pain within the first week post-vaccination in both treatment groups.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Full Analysis Population 1

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	378	377
Measure Type: Count of Participants; Unit of Measure: Participants
None	297 78.6%	282 74.8%
Mild	69 18.3%	73 19.4%
Mod/Severe	12 3.2%	22 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	The null hypothesis is allV3 is inferior (i.e., allV3 will have higher rates of moderate/severe injection site pain) to IIV3-HD in regards to the proportion of subjects having moderate or severe injection site pain in the first week post vaccination.
	Type of Statistical Test	Non-Inferiority
	Comments	The one-sided non-inferiority test with the alpha level set at 0.025 and non-inferiority margin of 5%, stratified by site.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-2.7
	Confidence Interval	(2-Sided) 95%; -5.8 to 0.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

2. Primary Outcome

Title	Number of Participants With Adverse Events of Clinical Interest, Population 2
Description	The frequency and descriptions of adverse events of clinical interest observed in the two treatment groups.
Time Frame	42 days post-vaccination and compared between the two groups.

Outcome Measure Data

Analysis Population Description

Full Analysis Population 2

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	378	379
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%

3. Primary Outcome

Title	Observed Serious Adverse Events in Both Treatment Groups, Population 2
Description	The frequency and descriptions of serious adverse events observed in the two treatment groups. No analytical analysis was completed.
Time Frame	42 days post-vaccination and compared between the two groups.

Outcome Measure Data

Analysis Population Description

Full Analysis Population 2

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	378	379
Measure Type: Number; Unit of Measure: SAE Events
Fall	2	0
Metastatic squamous cell	0	1
Post-operative ileus	0	1
Respiratory Failure	1	0
Stress induced cardiomyopathy	1	0
TIA	1	0
Chest Pain	0	1
Asthma exacerbation	1	0
Near syncope due to orthostasis	1	0
Pulmonary emboli	1	0
Small bowel obstruction	1	0
SAEs related to study product	0	0
SAEs not related to study product	9	3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The comparison of the number of participants with reported SAEs regardless of relationship to study product were made using 95% confidence intervals. Results were reported using exact binomial confidence intervals.
Method of Estimation	Estimation Parameter	Comparison of Frequencies
	Estimated Value	2.38
	Confidence Interval	(2-Sided) 95%; 1.09 to 4.47
	Estimation Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High-dose Influenza Vaccine (Fluzone® HD)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	The comparison of the number of participants with reported SAEs regardless of relationship to study product were made using 95% confidence intervals. Results were reported using exact binomial confidence intervals.
Method of Estimation	Estimation Parameter	Comparison of Frequencies
	Estimated Value	.79
	Confidence Interval	(2-Sided) 95%; 0.16 to 2.23
	Estimation Comments	[Not Specified]

4. Primary Outcome

Title	Number of Participants With H3N2 HAI Seroconversion
Description	H3N2 hemagglutination inhibition assay (HAI) seroconversion: The proportion of subjects achieving H3N2 seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer is > 1:10) in the respective season's vaccine
Time Frame	29 days post-vaccination

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	342	338
Measure Type: Count of Participants; Unit of Measure: Participants
	112 32.7%	130 38.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Influenza Vaccine, Adjuvanted (FLUAD®), High-Dose Influenza Vaccine (Fluzone HD)
	Comments	[Not Specified]
	Type of Statistical Test	Non-Inferiority
	Comments	This objective will be assessed using a one-sided noninferiority test with the alpha level set at 0.025 and noninferiority margin of 10%. The null hypothesis is the allV3 H3N2 seroconversion rate is inferior to IIV3-HD seroconversion rate.
Statistical Test of Hypothesis	P-Value	0.1245
	Comments	[Not Specified]
	Method	Cochran-Mantel-Haenszel
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	-.0579
	Confidence Interval	(1-Sided) 97.5%; -.1291
	Estimation Comments	The directional comparison was the lower bound of the confidence interval using a 10% non-inferiority margin.

5. Secondary Outcome

Title	Number of Participants With Local Reactions in Arm That Was Vaccinated - Full Study, Population 1
Description	Comparison of local reactions within the first week post-vaccination in both treatment groups.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Full Analysis Population 1

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		378	377
Measure Type: Count of Participants; Unit of Measure: Participants
Redness	None	348 92.1%	341 90.5%
	Mild	24 6.3%	23 6.1%
	Mod/Severe	6 1.6%	13 3.4%
Shoulder Pain	None	317 83.9%	326 86.5%
	Mild	44 11.6%	36 9.5%
	Mod/Severe	17 4.5%	15 4.0%
Swelling	None	335 88.6%	23 6.1%
	Mild	34 9.0%	26 6.9%
	Mod/Severe	9 2.4%	328 87.0%
Tenderness	None	201 53.2%	196 52.0%
	Mild	150 39.7%	160 42.4%
	Mod/Severe	27 7.1%	21 5.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Redness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.9
	Confidence Interval	(2-Sided) 98%; -5.0 to 1.0
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Shoulder Pain
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 98%; -3.1 to 4.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Swelling
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-3.7
	Confidence Interval	(2-Sided) 98%; -7.5 to -0.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Tenderness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 98%; -2.7 to 5.9
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

6. Secondary Outcome

Title	Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 65 - 79, Population 1
Description	Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Participants 65-79 years of age in Full Analysis Population 1

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1. FLUAD®: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1. Fluzone® High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		298	294
Measure Type: Count of Participants; Unit of Measure: Participants
Redness	None	274 91.9%	267 90.8%
	Mild	21 7.0%	17 5.8%
	Mod/Severe	3 1.0%	10 3.4%
Shoulder Pain	None	246 82.6%	249 84.7%
	Mild	36 12.1%	33 11.2%
	Mod/Severe	16 5.4%	12 4.1%
Swelling	None	264 88.6%	253 86.1%
	Mild	28 9.4%	22 7.5%
	Mod/Severe	6 2.0%	19 6.5%
Tenderness	None	157 52.7%	138 46.9%
	Mild	117 39.3%	137 46.6%
	Mod/Severe	24 8.1%	19 6.5%
Injection Site Pain	None	232 77.9%	210 71.4%
	Mild	56 18.8%	65 22.1%
	Mod/Severe	10 3.4%	19 6.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Redness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -5.2 to 0.2
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Shoulder Pain
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.3
	Confidence Interval	(2-Sided) 95%; -2.3 to 4.9
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Swelling
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-4.5
	Confidence Interval	(2-Sided) 95%; -8.1 to -1.1
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Tenderness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.6
	Confidence Interval	(2-Sided) 95%; -2.7 to 5.9
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Injection Site Pain
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-3.1
	Confidence Interval	(2-Sided) 95%; -6.9 to 0.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

7. Secondary Outcome

Title	Number of Participants With Local Reactions in Arm That Was Vaccinated - Ages 80 +, Population 1
Description	Comparison of local reactions within the first week post-vaccination in both treatment groups by age group.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Participants 80+ years of age in Full Analysis Population 1

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		80	83
Measure Type: Count of Participants; Unit of Measure: Participants
Redness	None	74 92.5%	74 89.2%
	Mild	3 3.8%	6 7.2%
	Mod/Severe	3 3.8%	3 3.6%
Shoulder Pain	None	71 88.8%	77 92.8%
	Mild	8 10.0%	3 3.6%
	Mod/Severe	1 1.3%	3 3.6%
Swelling	None	71 88.8%	75 90.4%
	Mild	6 7.5%	4 4.8%
	Mod/Severe	3 3.8%	4 4.8%
Tenderness	None	44 55.0%	58 69.9%
	Mild	33 41.3%	23 27.7%
	Mod/Severe	3 3.8%	2 2.4%
Injection Site Pain	None	65 81.3%	72 86.7%
	Mild	13 16.3%	8 9.6%
	Mod/Severe	2 2.5%	3 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Redness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -7.3 to 7.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Shoulder Pain
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 95%; -9.5 to 5.7
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Swelling
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -8.6 to 6.1
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Tenderness
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -5.7 to 8.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Injection Site Pain
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -7.9 to 5.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

8. Secondary Outcome

Title	Number of Participants With Systemic Reactions - Full Study Population, Population 1
Description	Comparison of systemic reactions within the first week post-vaccination in both treatment groups.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Full Analysis Population 1:

Four missing patient-reported outcome measures for "Fever" outcome.

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		378	377
Measure Type: Count of Participants; Unit of Measure: Participants
Arthralgia	Number Analyzed	378 participants	377 participants
	None	340 89.9%	346 91.8%
	Mild	20 5.3%	20 5.3%
	Mod/Severe	18 4.8%	11 2.9%
Chills/Shivering	Number Analyzed	378 participants	377 participants
	None	362 95.8%	363 96.3%
	Mild	13 3.4%	9 2.4%
	Mod/Severe	3 0.8%	5 1.3%
Diarrhea	Number Analyzed	378 participants	377 participants
	None	358 94.7%	359 95.2%
	Mild	15 4.0%	9 2.4%
	Mod/Severe	5 1.3%	9 2.4%
Fatigue	Number Analyzed	378 participants	377 participants
	None	319 84.4%	337 89.4%
	Mild	32 8.5%	25 6.6%
	Mod/Severe	27 7.1%	15 4.0%
Fever	Number Analyzed	378 participants	373 participants
	None	366 96.8%	358 96.0%
	Mild	11 2.9%	12 3.2%
	Mod/Severe	1 0.3%	3 0.8%
Headache	Number Analyzed	378 participants	377 participants
	None	335 88.6%	338 89.7%
	Mild	36 9.5%	31 8.2%
	Mod/Severe	7 1.9%	8 2.1%
Malaise	Number Analyzed	378 participants	377 participants
	None	332 87.8%	344 91.2%
	Mild	28 7.4%	22 5.8%
	Mod/Severe	18 4.8%	11 2.9%
Myalgia	Number Analyzed	378 participants	377 participants
	None	334 88.4%	338 89.7%
	Mild	25 6.6%	22 5.8%
	Mod/Severe	19 5.0%	17 4.5%
Nausea	Number Analyzed	378 participants	377 participants
	None	357 94.4%	362 96.0%
	Mild	19 5.0%	10 2.7%
	Mod/Severe	2 0.5%	5 1.3%
Vomiting	Number Analyzed	378 participants	377 participants
	None	374 98.9%	374 99.2%
	Mild	2 0.5%	1 0.3%
	Mod/Severe	2 0.5%	2 0.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Arthralgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 98%; -1.7 to 5.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Chills/Shivering
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 98%; -2.8 to 2.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Diarrhea
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.1
	Confidence Interval	(2-Sided) 98%; -4.0 to 1.5
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fatigue
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	3.2
	Confidence Interval	(2-Sided) 98%; -0.8 to 7.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fever
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 98%; -2.5 to 2.0
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Headache
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 98%; -3.0 to 2.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Malaise
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.8
	Confidence Interval	(2-Sided) 98%; -1.7 to 5.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Myalgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 98%; -3.3 to 4.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Nausea
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.8
	Confidence Interval	(2-Sided) 98%; -3.1 to 1.6
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Vomiting
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.01 level to adjust for multiple comparisons.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 98%; -1.8 to 1.8
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

9. Secondary Outcome

Title	Number of Participants With System Reactions - Ages 65 - 79, Population 1
Description	Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Participants 65-79 years of age in Full Analysis Population 1: Three missing "Fever" outcome values for the Fluzone HD group.

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		298	294
Measure Type: Count of Participants; Unit of Measure: Participants
Arthralgia	Number Analyzed	298 participants	294 participants
	None	266 89.3%	266 90.5%
	Mild	16 5.4%	19 6.5%
	Mod/Severe	16 5.4%	9 3.1%
Chills/Shivering	Number Analyzed	298 participants	294 participants
	None	283 95.0%	282 95.9%
	Mild	12 4.0%	7 2.4%
	Mod/Severe	3 1.0%	5 1.7%
Diarrhea	Number Analyzed	298 participants	294 participants
	None	280 94.0%	280 95.2%
	Mild	13 4.4%	7 2.4%
	Mod/Severe	5 1.7%	7 2.4%
Fatigue	Number Analyzed	298 participants	294 participants
	None	248 83.2%	258 87.8%
	Mild	27 9.1%	22 7.5%
	Mod/Severe	23 7.7%	14 4.8%
Fever	Number Analyzed	298 participants	291 participants
	None	288 96.6%	278 95.5%
	Mild	10 3.4%	10 3.4%
	Mod/Severe	0 0.0%	3 1.0%
Headache	Number Analyzed	298 participants	294 participants
	None	259 86.9%	257 87.4%
	Mild	32 10.7%	29 9.9%
	Mod/Severe	7 2.3%	8 2.7%
Malaise	Number Analyzed	298 participants	294 participants
	None	260 87.2%	264 89.8%
	Mild	24 8.1%	19 6.5%
	Mod/Severe	14 4.7%	11 3.7%
Myalgia	Number Analyzed	298 participants	294 participants
	None	262 87.9%	261 88.8%
	Mild	20 6.7%	19 6.5%
	Mod/Severe	16 5.4%	14 4.8%
Nausea	Number Analyzed	298 participants	294 participants
	None	280 94.0%	280 95.2%
	Mild	16 5.4%	9 3.1%
	Mod/Severe	2 0.7%	5 1.7%
Vomiting	Number Analyzed	298 participants	294 participants
	None	294 98.7%	291 99.0%
	Mild	2 0.7%	1 0.3%
	Mod/Severe	2 0.7%	2 0.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Arthralgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	2.3
	Confidence Interval	(2-Sided) 95%; -1.1 to 5.8
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Chills/Shivering
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.0 to 2.0
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Diarrhea
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -3.5 to 1.8
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fatigue
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; -1.1 to 7.0
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fever
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -3.0 to -0.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Headache
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -3.2 to 2.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Malaise
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -2.5 to 4.5
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Myalgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -3.1 to 4.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Nausea
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-1.0
	Confidence Interval	(2-Sided) 95%; -3.3 to 1.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Vomiting
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-0.0
	Confidence Interval	(2-Sided) 95%; -1.8 to 1.8
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

10. Secondary Outcome

Title	Number of Participants With System Reactions - Ages 80 +, Population 1
Description	Comparison of systemic reactions within the first week post-vaccination in both treatment groups by age group.
Time Frame	Days 1 through 8 post-vaccination

Outcome Measure Data

Analysis Population Description

Participants 80+ years of age in Full Analysis Population 1: One missing "Fever" outcome value in the Fluzone HD group.

No statistical analysis completed on following Outcomes: Chills/Shivering, Headache, Nausea, Vomiting because none reported in this age group.

Arm/Group Title		Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:		In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed		80	83
Measure Type: Count of Participants; Unit of Measure: Participants
Arthralgia	Number Analyzed	80 participants	83 participants
	None	74 92.5%	80 96.4%
	Mild	4 5.0%	1 1.2%
	Mod/Severe	2 2.5%	2 2.4%
Chills/Shivering	Number Analyzed	80 participants	83 participants
	None	79 98.8%	81 97.6%
	Mild	1 1.3%	2 2.4%
	Mod/Severe	0 0.0%	0 0.0%
Diarrhea	Number Analyzed	80 participants	83 participants
	None	78 97.5%	79 95.2%
	Mild	2 2.5%	2 2.4%
	Mod/Severe	0 0.0%	2 2.4%
Fatigue	Number Analyzed	80 participants	83 participants
	None	71 88.8%	79 95.2%
	Mild	5 6.3%	3 3.6%
	Mod/Severe	4 5.0%	1 1.2%
Fever	Number Analyzed	80 participants	82 participants
	None	78 97.5%	80 97.6%
	Mild	1 1.3%	2 2.4%
	Mod/Severe	1 1.3%	0 0.0%
Headache	Number Analyzed	80 participants	83 participants
	None	76 95.0%	81 97.6%
	Mild	4 5.0%	2 2.4%
	Mod/Severe	0 0.0%	0 0.0%
Malaise	Number Analyzed	80 participants	83 participants
	None	72 90.0%	80 96.4%
	Mild	4 5.0%	3 3.6%
	Mod/Severe	4 5.0%	0 0.0%
Myalgia	Number Analyzed	80 participants	83 participants
	None	72 90.0%	77 92.8%
	Mild	5 6.3%	3 3.6%
	Mod/Severe	3 3.8%	3 3.6%
Nausea	Number Analyzed	80 participants	83 participants
	None	77 96.3%	82 98.8%
	Mild	3 3.8%	1 1.2%
	Mod/Severe	0 0.0%	0 0.0%
Vomiting	Number Analyzed	80 participants	83 participants
	None	80 100.0%	83 100.0%
	Mild	0 0.0%	0 0.0%
	Mod/Severe	0 0.0%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Arthralgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -7.2 to 6.4
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Diarrhea
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -8.1 to -0.6
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fatigue
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	3.7
	Confidence Interval	(2-Sided) 95%; -3.6 to 10.9
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Fever
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	1.2
	Confidence Interval	(2-Sided) 95%; -2.4 to 6.6
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Malaise
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; 2.0 to 12.2
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Myalgia
	Type of Statistical Test	Non-Inferiority
	Comments	Site-stratified, 5% noninferiority test with a one-sided alpha at the 0.025 level.
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.1
	Confidence Interval	(2-Sided) 95%; -7.3 to 7.3
	Estimation Comments	The upper bound of a stratified Newcombe binomial confidence interval with Cochran-Mantel-Haenszel weighting of the difference was used.

11. Secondary Outcome

Title	Quality of Life - Late Life Function & Disability Instrument - Full Population
Description	Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

LLFDI data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	138	141
Mean (95% Confidence Interval); Unit of Measure: score on a scale
Activity Limitation	-1.43; (-2.20 to -0.66)	-2.25; (-2.99 to -1.51)
Daily Activities	-1.26; (-2.04 to -0.48)	-2.06; (-2.77 to -1.35)
Basic Mobility	-1.37; (-2.06 to -0.68)	-2.43; (-3.14 to -1.72)
Participation Restriction	-0.86; (-1.57 to -0.15)	-1.58; (-2.31 to -0.85)
Social Roles	-0.77; (-1.55 to 0.01)	-1.80; (-2.58 to -1.02)
Instrumental Roles	-1.08; (-1.82 to -0.34)	-1.66; (-2.41 to -0.91)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Activity Limitation Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.5862
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Daily Activities Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.5648
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Basic Mobility Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.4196
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Participation Restriction Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.2418
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Social Roles Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.0746
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Instrumental Roles Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.5497
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

12. Secondary Outcome

Title	Quality of Life - Late Life Function & Disability Instrument - Ages 65 - 79
Description	Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 65-79 years of age. LLFDI data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	119	120
Mean (95% Confidence Interval); Unit of Measure: score on a scale
Activity Limitation	-1.35; (-2.20 to -0.50)	-2.12; (-2.91 to -1.33)
Daily Activities	-1.16; (-2.02 to -0.30)	-1.88; (-2.60 to -1.15)
Basic Mobility	-1.33; (-2.09 to -.056)	-2.29; (-3.03 to -1.55)
Participation Restriction	-0.81; (-1.52 to -0.10)	-1.69; (-2.44 to -0.93)
Social Roles	-0.66; (-1.46 to 0.14)	-1.98; (-2.82 to -1.14)
Instrumental Roles	-1.00; (-1.74 to -0.27)	-1.70; (-2.47 to -0.93)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Activity Limitation Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.6278
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Daily Activities Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.5622
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Basic Mobility Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.5538
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Participation Restriction Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.2310
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Social Roles Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.0435
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Instrumental Roles Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.6519
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

13. Secondary Outcome

Title	Quality of Life - Late Life Function & Disability Instrument - Ages 80 +
Description	Change in scores on the Late Life Function & Disability Instrument pre-vaccination to post-vaccination (Day 1 - Day 3) compared between the vaccination groups (Year 1 only). Response choices are ranked 1-5, High Scores indicate better outcomes. The Function/Activity Scale measured the amount of difficulty in completing a range of activities, or the amount of help required in doing an activity due to physical or mental heath. : None (5); A little (4) ; Some (3), Quite a lot (2), and Cannot Do (1). The Disability/Participation Scale measured participation levels in social, family, and community activities due to physical or mental health. Each question has two parts. For the first part of the question, response choices include: Very often (5), Often (4), Once in a while (3), Almost never (2), Never (1). For the second part of the question, response choices include: Not at all (5), A little (4), Somewhat (3), A lot (2), and Completely (1).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 80+ years of age. LLFDI data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	19	21
Mean (95% Confidence Interval); Unit of Measure: score on a scale
Activity Limitation	-1.94; (-3.81 to -0.08)	-2.99; (-5.25 to -0.74)
Daily Activities	-1.86; (-3.74 to 0.03)	-3.13; (-5.65 to -0.61)
Basic Mobility	-1.62; (-3.22 to -0.02)	-3.23; (-5.58 to -0.88)
Participation Restriction	-1.17; (-4.00 to 1.67)	-0.97; (-3.54 to 1.60)
Social Roles	-1.45; (-4.31 to 1.41)	-0.72; (-2.98 to 1.53)
Instrumental Roles	-1.54; (-4.49 to 1.42)	-1.44; (-4.10 to 1.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Activity Limitation Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7483
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Daily Activities Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7483
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Basic Mobility Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.4953
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Participation Restriction Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.8669
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Social Roles Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.8451
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	Instrumental Roles Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7376
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

14. Secondary Outcome

Title	Quality of Life - EQ-5D-5L -Full Population
Description	Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

EQ-5D-5L data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	378	377
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-0.054; (-0.064 to -0.044)	-0.053; (-0.063 to -0.044)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	US Index Score Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7407
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

15. Secondary Outcome

Title	Quality of Life - EQ-5D-5L - Ages 65 - 79
Description	Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 65-79 years of age. EQ-5D-5L data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	298	296
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-0.054; (-0.065 to -0.042)	-0.051; (-0.062 to -0.040)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	US Index Score Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.4032
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

16. Secondary Outcome

Title	Quality of Life - EQ-5D-5L - Ages 80 +
Description	Change in scores on the EuroQOL 5 dimensions-5 level (EQ-5D-5L) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only) Responses on the EQ-5D-5L measure is converted to a Utility Index that ranges from -0.109 (worst health) to 1.000 (best health).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 80+ years of age. EQ-5D-5L data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	80	83
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-0.055; (-0.074 to -0.035)	-0.062; (-0.083 to -0.042)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	US Index Score Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.4079
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

17. Secondary Outcome

Title	Quality of Life - EQ VAS -Full Population
Description	Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

EQ VAS data collected for only one year.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	378	377
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-2.222; (-3.379 to -1.065)	-2.496; (-3.452 to -1.539)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	EQ VAS Changes for Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.01 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7948
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

18. Secondary Outcome

Title	Quality of Life - EQ VAS - Ages 65 - 79
Description	Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 65-79 years of age.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	298	296
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-2.474; (-3.876 to -1.071)	-2.791; (-3.923 to -1.658)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	EQ VAS Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. Alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.7953
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

19. Secondary Outcome

Title	Quality of Life - EQ VAS - Ages 80 +
Description	Change in scores on the EuroQOL visual analogue scale (EQ VAS) pre-vaccination and post-vaccination compared between the vaccination groups and age group (Year 1 only). The EQ VAS records the respondent's self-rated health on a 20 cm vertical, visual analogue scale with endpoints labelled 'the best health you can imagine' (100) and 'the worst health you can imagine' (0).
Time Frame	Pre-vaccination (Day 1), 2 days post-vaccination (Day 3)

Outcome Measure Data

Analysis Population Description

Participants 80+ years of age.

Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)	High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	80	83
Mean (95% Confidence Interval); Unit of Measure: Change in score
	-1.295; (-2.966 to 0.377)	-1.463; (-3.163 to 0.237)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Adjuvanted Influenza Vaccine (FLUAD®), High-dose Influenza Vaccine (Fluzone® HD)
	Comments	EQ VAS Changes from Day 1 to Day 3 Group Comparisons
	Type of Statistical Test	Superiority
	Comments	Non-parametric testing was used to evaluate the changes from baseline to compare between groups. A two-sided alpha level set at 0.05 with no adjustments set for multiple comparisons.
Statistical Test of Hypothesis	P-Value	0.9329
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

20. Secondary Outcome

Title	Seroconversion - 65 and Older
Description	The proportion of subjects achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	342	338
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	28.1; (23.4 to 33.2)	26.6; (22.0 to 31.7)
Influenza B	18.7; (14.7 to 23.3)	23.4; (19.0 to 28.3)

21. Secondary Outcome

Title	Seroprotection - 65 and Older
Description	Proportion of subjects with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	342	338
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1 - Baseline	69.6; (64.4 to 74.4)	66.9; (61.6 to 71.8)
A/H1N1 - Post-vaccination	83.3; (79.0 to 87.1)	83.4; (79.0 to 87.2)
A/H3N2 - Baseline	66.7; (61.4 to 71.6)	65.7; (60.4 to 70.7)
A/H3N2 - Post-vaccination	89.8; (86.1 to 92.7)	88.5; (84.6 to 91.6)
Influenza B - Baseline	24.6; (20.1 to 29.5)	26.9; (22.3 to 32.0)
Influenza B - Post-vaccination	44.2; (38.8 to 49.6)	48.8; (43.4 to 54.3)

22. Secondary Outcome

Title	Geometric Mean HAI Titer - 65 and Older
Description	The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	342	338
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: GMT
A/H1N1 - Baseline	51.8; (44.5 to 60.3)	50.8; (43.4 to 59.4)
A/H1N1 - Post-vaccination	100.0; (86.6 to 115.6)	98.0; (84.6 to 113.6)
A/H3N2 - Baseline	63.4; (52.8 to 76.1)	58.5; (48.4 to 70.7)
A/H3N2 - Post-vaccination	141.7; (123.2 to 162.9)	177.3; (152.7 to 205.9)
Influenza B - Baseline	13.4; (11.9 to 15.0)	14.7; (12.9 to 16.7)
Influenza B - Post-vaccination	21.6; (18.5 to 25.2)	27.5; (23.5 to 32.3)

23. Secondary Outcome

Title	Seroconversion - Ages 65-79
Description	The proportion of subjects aged 65-79 achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	269	261
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	29.7; (24.3 to 35.6)	27.2; (21.9 to 33.0)
A/H3N2	34.2; (28.5 to 40.2)	39.5; (33.5 to 45.7)
Influenza B	19.0; (14.5 to 24.2)	26.1; (20.8 to 31.8)

24. Secondary Outcome

Title	Seroconversion - Ages 80 and Older
Description	The proportion of subjects ages 80 and older achieving seroconversion at day 29 (an HAI titer > 1:40 at day 29 if the baseline titer is < 1:10 or a four-fold rise in HAI titer if the baseline titer
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	73	77
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1	21.9; (13.1 to 33.1)	24.7; (15.6 to 35.8)
A/H3N2	27.4; (17.6 to 39.1)	35.1; (24.5 to 46.7)
Influenza B	17.8; (9.8 to 28.5)	14.3; (7.4 to 24.1)

25. Secondary Outcome

Title	Seroprotection - Ages 65-79
Description	Proportion of subjects ages 65-79 with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	269	261
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1 - Baseline	69.9; (64.0 to 75.3)	65.5; (59.4 to 71.2)
A/H1N1 - Post-vaccination	83.6; (78.7 to 87.8)	82.8; (77.6 to 87.1)
A/H3N2 - Baseline	67.3; (61.3 to 72.8)	65.5; (59.4 to 71.2)
A/H3N2 - Post-vaccination	91.4; (87.4 to 94.4)	88.1; (83.6 to 91.7)
Influenza B - Baseline	22.3; (17.5 to 27.8)	19.9; (15.3 to 25.3)
Influenza B - Post-vaccination	42.4; (36.4 to 48.5)	45.2; (39.1 to 51.5)

26. Secondary Outcome

Title	Seroprotection - Ages 80 and Older
Description	Proportion of subjects ages 80 and older with a seroprotective HAI titer (≥ 1:40) pre- and post-immunization at day 29 for each IIV antigen in the respective season's vaccine
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	73	77
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
A/H1N1 - Baseline	68.5; (56.6 to 78.7)	71.4; (60.0 to 81.0)
A/H1N1 - Post-vaccination	82.2; (71.5 to 89.9)	85.7; (75.9 to 92.4)
A/H3N2 - Baseline	64.4; (52.3 to 75.1)	66.2; (54.6 to 76.5)
A/H3N2 - Post-vaccination	83.6; (73.0 to 91.0)	89.6; (80.6 to 95.2)
Influenza B - Baseline	32.9; (22.3 to 44.8)	50.6; (39.0 to 62.2)
Influenza B - Post-vaccination	50.7; (38.7 to 62.5)	61.0; (49.2 to 71.8)

27. Secondary Outcome

Title	Geometric Mean HAI Titer - Ages 65-79
Description	The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 65-79
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	269	261
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: GMT
A/H1N1 - Baseline	52.5; (44.3 to 62.2)	49.5; (41.4 to 59.0)
A/H1N1 - Post-vaccination	108.8; (92.1 to 128.5)	100.9; (84.9 to 119.9)
A/H3N2 - Baseline	63.3; (51.7 to 77.5)	56.4; (45.5 to 69.8)
A/H3N2 - Post-vaccination	145.3; (124.3 to 169.7)	184.4; (155.2 to 219.1)
Influenza B - Baseline	12.2; (10.8 to 13.8)	11.8; (10.3 to 13.4)
Influenza B - Post-vaccination	20.3; (17.2 to 24.1)	23.8; (20.0 to 28.4)

28. Secondary Outcome

Title	Geometric Mean HAI Titer - Ages 80 and Older
Description	The geometric mean HAI titer (GMT) for each IIV antigen in the respective season's vaccine for ages 80 and older
Time Frame	Day 29 (28 days post-vaccination)

Outcome Measure Data

Analysis Population Description

Immunogenicity Population - subjects receiving the study intervention. Participants analyzed include those that provided baseline and Visit 4 blood draws of acceptable volume and quality within the protocol-defined time frame with no protocol violations affecting immunogenicity.

Arm/Group Title	Influenza Vaccine, Adjuvanted (FLUAD®)	High-Dose Influenza Vaccine (Fluzone HD)
Arm/Group Description:	In the study arm, subjects will receive a single dose of FLUAD adjuvanted influenza vaccine during Visit 1. FLUAD: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine	In the study arm, subjects will receive a single dose of Fluzone High-Dose influenza vaccine during Visit 1. Fluzone High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
Overall Number of Participants Analyzed	73	77
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: GMT
A/H1N1 - Baseline	49.3; (35.1 to 69.3)	55.6; (39.2 to 78.8)
A/H1N1 - Post-vaccination	73.4; (55.2 to 97.7)	88.7; (66.7 to 118.0)
A/H3N2 - Baseline	63.7; (41.4 to 98.0)	66.5; (43.9 to 101.0)
A/H3N2 - Post-vaccination	129.2; (93.4 to 178.8)	155.0; (114.2 to 210.5)
Influenza B - Baseline	18.7; (14.6 to 24.0)	31.2; (23.2 to 42.1)
Influenza B - Post-vaccination	27.0; (19.0 to 38.2)	45.0; (31.8 to 63.5)

Adverse Events

Time Frame	Adverse Events, Serious Adverse Events, and All-Cause Mortality rates were collected 42 days post vaccination. Serious Adverse Events and Mortality Rates were collected up to 181 days for the longer-term immunogenicity subset
Adverse Event Reporting Description	The two reported deaths occurred >42 days post vaccination
Arm/Group Title	Adjuvanted Influenza Vaccine (FLUAD®)		High-dose Influenza Vaccine (Fluzone® HD)
Arm/Group Description	In the study arm, subjects will receive a single dose of FLUAD® adjuvanted influenza vaccine during Visit 1. FLUAD®: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine		In the study arm, subjects will receive a single dose of Fluzone® High-Dose influenza vaccine during Visit 1. Fluzone® High-Dose: Advisory Committee on Immunization Practices (ACIP) Recommended Vaccine
All-Cause Mortality
	Adjuvanted Influenza Vaccine (FLUAD®)		High-dose Influenza Vaccine (Fluzone® HD)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	1/378 (0.26%)		1/379 (0.26%)
Serious Adverse Events
	Adjuvanted Influenza Vaccine (FLUAD®)		High-dose Influenza Vaccine (Fluzone® HD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/378 (2.65%)		4/379 (1.06%)
Blood and lymphatic system disorders
Metastatic squamous cell *	0/378 (0.00%)	0	1/379 (0.26%)	1
Cardiac disorders
Chest Pain *	1/378 (0.26%)	1	1/379 (0.26%)	1
Stressed induced cardiomyopathy *	1/378 (0.26%)	1	0/379 (0.00%)	0
Gastrointestinal disorders
Post-operative ileus *	0/378 (0.00%)	0	1/379 (0.26%)	1
Small bowel obstruction *	1/378 (0.26%)	1	1/379 (0.26%)	1
General disorders
Fall *	2/378 (0.53%)	2	0/379 (0.00%)	0
Nervous system disorders
TIA *	1/378 (0.26%)	1	0/379 (0.00%)	0
Near syncope due to orthostatic *	1/378 (0.26%)	1	0/379 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Respiratory Failure *	1/378 (0.26%)	1	0/379 (0.00%)	0
Asthma exacerbation *	1/378 (0.26%)	1	0/379 (0.00%)	0
Pulmonary emboli *	1/378 (0.26%)	1	0/379 (0.00%)	0
* Indicates events were collected by non-systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Adjuvanted Influenza Vaccine (FLUAD®)		High-dose Influenza Vaccine (Fluzone® HD)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/378 (3.97%)		19/379 (5.01%)
Respiratory, thoracic and mediastinal disorders
Cold * [1]	15/378 (3.97%)	15	19/379 (5.01%)	19
* Indicates events were collected by non-systematic assessment; [1] Cold symptoms

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Kenneth Schmader
• Organization: Duke University
• Phone: 919-660-7572
• EMail: kenneth.schmader@duke.edu

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Schmader KE, Liu CK, Harrington T, Rountree W, Auerbach H, Walter EB, Barnett ED, Schlaudecker EP, Todd CA, Poniewierski M, Staat MA, Wodi P, Broder KR. Safety, Reactogenicity, and Health-Related Quality of Life After Trivalent Adjuvanted vs Trivalent High-Dose Inactivated Influenza Vaccines in Older Adults: A Randomized Clinical Trial. JAMA Netw Open. 2021 Jan 4;4(1):e2031266. doi: 10.1001/jamanetworkopen.2020.31266.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT03183908
• Other Study ID Numbers: Pro00083845
• First Submitted: June 7, 2017
• First Posted: June 12, 2017
• Results First Submitted: February 13, 2020
• Results First Posted: March 30, 2021
• Last Update Posted: March 30, 2021