OLIVE: Open-Label Influenza Vaccine Evaluation

• Sponsor: Marshfield Clinic Research Foundation (Other)
• Overall Status: Completed
• CT.gov ID: NCT02872311
• Collaborator: Centers for Disease Control and Prevention (U.S. Fed)
• Enrollment: 179
• Location: 1
• Arms: 5
• Duration (Months): 24
• Patients Per Site Per Month: 7.5

Study Details

Study Description

Brief Summary

This is an open-label, randomized trial in up to 210 adults aged 65-74 years to evaluate the immune response to consecutive influenza vaccination across 2 seasons. Participants will be randomized to receive 1 of 3 licensed and recommended vaccines in the first year; 2 arms will receive the same vaccination in the second year and the third arm will be randomized again to 1 of 3 licensed vaccines. All participants will have pre and post-vaccination serum blood draws for a total of 6 draws over 18 months.

Condition or Disease	Intervention/Treatment	Phase
Immune Response	Biological: High Dose Influenza vaccine; Biological: Adjuvanted Influenza vaccine; Biological: Standard Dose Influenza vaccine; Biological: Recombinant Influenza vaccine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 179 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Open-Label, Randomized Study of Immune Response to Licensed Influenza Vaccines in Adults 65-74 Years of Age (US Flu Vaccine Effectiveness Serologic Study, 2016-17 and 2017-18)
• Study Start Date: Sep 1, 2016
• Actual Primary Completion Date: Apr 1, 2018
• Actual Study Completion Date: Sep 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: High Dose Influenza Vaccine This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	Biological: High Dose Influenza vaccine; Licensed and FDA approved Fluzone HD vaccine to be administered to study participants; Other Names: Fluzone HD
Active Comparator: Adjuvanted Influenza Vaccine This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	Biological: Adjuvanted Influenza vaccine; Licensed and FDA approved FluAd vaccine to be administered to study participants; Other Names: FluAd
Active Comparator: Standard Dose Influenza Vaccine+HD This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study.	Biological: High Dose Influenza vaccine; Licensed and FDA approved Fluzone HD vaccine to be administered to study participants; Other Names: Fluzone HD ; Biological: Standard Dose Influenza vaccine; Licensed and FDA approved Fluvirin vaccine to be administered to study participants; Other Names: Fluvirin Standard Dose
Active Comparator: Standard Dose Influenza Vaccine +Adj This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study.	Biological: Adjuvanted Influenza vaccine; Licensed and FDA approved FluAd vaccine to be administered to study participants; Other Names: FluAd ; Biological: Standard Dose Influenza vaccine; Licensed and FDA approved Fluvirin vaccine to be administered to study participants; Other Names: Fluvirin Standard Dose
Active Comparator: Standard Dose Influenza Vaccine+Recomb This group will be administered a standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study.	Biological: Standard Dose Influenza vaccine; Licensed and FDA approved Fluvirin vaccine to be administered to study participants; Other Names: Fluvirin Standard Dose ; Biological: Recombinant Influenza vaccine; Licensed and FDA approved FluBlok vaccine to be administered to study participants; Other Names: FluBlok

Outcome Measures

Primary Outcome Measures

1. HI Titers, HD vs. AD, Yr 1 Day 28 Post Vaccination [Year 1, Day 28 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 28 days post vaccination 2016-17

2. HI Titers, HD vs. AD, Yr 1 Day 182 Post Vaccination [Year 1, Day 182 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 182 days post vaccination 2016-17

3. HI Titers, HD vs. AD, Yr 1 Day 365 Post Vaccination [Year 1, Day 365 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 365 days post vaccination 2016-17

4. HI Titers, HD vs. AD, Yr 2 Day 28 Post Vaccination [Year 2, Day 28 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 28 days post vaccination 2017-18

5. HI Titers, HD vs. AD, Yr 2 Day 182 Post Vaccination [Year 2, Day 182 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 182 days post vaccination 2017-18

Secondary Outcome Measures

1. HI Response by Prior Season Vaccination, Yr 1, Day 28 Post Vaccination [Year 1, Day 28 post vaccination]

   Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 28 days post vaccination, 2016-17

2. HI Response by Prior Season Vaccination, Yr 1, Day 182 Post Vaccination [Year 1, Day 182 post vaccination]

   Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 182 days post vaccination, 2016-17

3. HI Response by Prior Season Vaccination, Yr 1, Day 365 Post Vaccination [Year 1, Day 365 post vaccination]

   Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 365 days post vaccination, 2016-17

4. MN Titers, HD vs. AD, Year 1, Day 28 Post Vaccination [Year 1, Day 28 post vaccination]

   Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 28 days post vaccination, 2016-17

5. MN Titers, HD vs. AD, Year 1, Day 182 Post Vaccination [Year 1, Day 182 post vaccination]

   Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 182 days post vaccination, 2016-17

6. MN Titers, HD vs. AD, Year 1, Day 365 Post Vaccination [Year 1, Day 365 post vaccination]

   Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 365 days post vaccination, 2016-17

7. MN Titers (A/Hong Kong (Siat Cell)), HD vs. AD, Year 2, Day 28 Post Vaccination [Year 2, Day 28 post vaccination]

   Microneutralization antibody titers to vaccine virus (A/Hong Kong (siat cell) among high dose and adjuvanted vaccine recipients 28 days post vaccination, 2017-18

8. HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, Year 2, Day 28 Post Vaccination [Year 2, Day 28 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses among adjuvant, high dose and recombinant recipients with prior season standard dose vaccine at 28 days post vaccination 2017-18

9. HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, Year 2, Day 182 Post Vaccination [Year 2, Day 182 post vaccination]

   Hemagglutination Inhibition (HI) titers to vaccine viruses among adjuvant, high dose and recombinant recipients with prior season standard dose vaccine at 182 days post vaccination 2017-18

10. HI Titers, IIV+AD or HD vs. Sequential AD or HD, Year 2, Day 28 Post Vaccination [Year 2, Day 28 post vaccination]

    Hemagglutination inhibition (HI) titers among HD and AD based on prior season vaccination (standard or sequential same vaccination) at 28 days after vaccination, 2017-18

11. HI Titers, IIV+AD or HD vs. Sequential AD or HD, Year 2, Day 182 Post Vaccination [Year 2, Day 182 post vaccination]

    Hemagglutination inhibition (HI) titers among HD and AD based on prior season vaccination (standard or sequential same vaccination) at 182 days after vaccination, 2017-18

12. Number of Participants With Vaccine Failure, Year 1 [Year 1, Post season]

    Number of Participants with Vaccine Failure in Year 1 by vaccine type

13. Number of Participants With Vaccine Failure, Year 2 [Year 2, Post season]

    Number of Participants with Vaccine Failure in Year 2 by two-year vaccine history

Eligibility Criteria

Criteria

• Ages Eligible for Study: 65 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 65-74 years at the time of study enrollment and are ambulatory and live in selected Wisconsin community or surrounding communities.

• Willing and able to give informed consent prior to study enrollment

• Able to comply with study requirements.

Exclusion Criteria:

• Prior receipt of 2016-17 influenza vaccine

• Current participation in another clinical trial

• Presence of a contraindication to influenza vaccine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin	United States	54449

Sponsors and Collaborators

• Marshfield Clinic Research Foundation
• Centers for Disease Control and Prevention

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 15, 2017

More Information

Publications

None provided.

• Responsible Party: Huong McLean, PhD, Research Scientist, Marshfield Clinic Research Foundation
• ClinicalTrials.gov Identifier: NCT02872311
• Other Study ID Numbers: MCL10416
• First Posted: Aug 19, 2016
• Last Update Posted: Dec 19, 2019
• Last Verified: Dec 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Huong McLean, PhD, Research Scientist, Marshfield Clinic Research Foundation: Vaccine; Influenza; High Dose; Adjuvanted; Recombinant
• Additional relevant MeSH terms: Influenza, Human; Vaccines

Study Results

Participant Flow

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine	Standard+High Dose	Standard+Adjuvanted	Standard+Recombinant
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and high dose influenza vaccination (0.5mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. Recombinant Influenza vaccine: Licensed and FDA approved FluBlok vaccine to be administered to study participants
Period Title: Overall Study
STARTED	59	60	20	20	20
COMPLETED	55	58	19	20	20
NOT COMPLETED	4	2	1	0	0

Baseline Characteristics

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine	Standard Dose Influenza Vaccine+HD	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+Recomb	Total
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants	This group will be administered a standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants Recombinant Influenza vaccine: Licensed and FDA approved FluBlok vaccine to be administered to study participants	Total of all reporting groups
Overall Participants	55	58	19	20	20	172
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	70 (2.7)	69.6 (2.6)	69.4 (2.9)	69.2 (2.2)	70 (2.7)	70 (2.6)
Sex: Female, Male (Count of Participants)
Female	26 47.3%	33 56.9%	10 52.6%	12 60%	9 45%	90 52.3%
Male	29 52.7%	25 43.1%	9 47.4%	8 40%	11 55%	82 47.7%
Race/Ethnicity, Customized (Count of Participants)
Race : White	55 100%	58 100%	19 100%	20 100%	20 100%	172 100%
Region of Enrollment (Count of Participants)
United States	55 100%	58 100%	19 100%	20 100%	20 100%	172 100%

Outcome Measures

1. Primary Outcome

Title	HI Titers, HD vs. AD, Yr 1 Day 28 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 28 days post vaccination 2016-17
Time Frame	Year 1, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

This primary objective evaluated only recipients in the arms receiving high dose and adjuvanted vaccine in year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H1/California	175	117
A/H3/Hong Kong	144	118
B/Brisbane(Victoria)	166	81

2. Primary Outcome

Title	HI Titers, HD vs. AD, Yr 1 Day 182 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 182 days post vaccination 2016-17
Time Frame	Year 1, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

This primary objective evaluated only recipients in the arms receiving high dose and adjuvanted vaccine in year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H1/California	83	56
A/H3/Hong Kong	83	68
B/Brisbane(Victoria)	61	44

3. Primary Outcome

Title	HI Titers, HD vs. AD, Yr 1 Day 365 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 365 days post vaccination 2016-17
Time Frame	Year 1, Day 365 post vaccination

Outcome Measure Data

Analysis Population Description

This primary objective evaluated only recipients in the arms receiving high dose and adjuvanted vaccine in year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H1/California	54	44
A/H3/Hong Kong	75	75
B/Brisbane(Victoria)	36	24

4. Primary Outcome

Title	HI Titers, HD vs. AD, Yr 2 Day 28 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 28 days post vaccination 2017-18
Time Frame	Year 2, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

This primary objective evaluated only recipients in the arms receiving high dose and adjuvanted vaccine in year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H1/Michigan	83	101
A/H3/Hong Kong	158	158
B/Brisbane(Victoria)	63	45

5. Primary Outcome

Title	HI Titers, HD vs. AD, Yr 2 Day 182 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses for high dose and adjuvanted vaccine recipients at 182 days post vaccination 2017-18
Time Frame	Year 2, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

This primary objective evaluated only recipients in the arms receiving high dose and adjuvanted vaccine in year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H1/Michigan	46	44
A/H3/Hong Kong	101	124
B/Brisbane(Victoria)	44	30

6. Secondary Outcome

Title	HI Response by Prior Season Vaccination, Yr 1, Day 28 Post Vaccination
Description	Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 28 days post vaccination, 2016-17
Time Frame	Year 1, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients by prior season vaccination status.

Arm/Group Title	IIV-ADJ	IIV-HD	None-ADJ	None-HD
Arm/Group Description	2015-16 Standard dose vaccine recipient who received adjuvanted vaccine in the study in 2016-17	2015-16 Standard dose vaccine recipient who received high dose vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received adjuvanted vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received high dose vaccine in the study in 2016-17
Measure Participants	44	40	14	15
A/H1/California	116	136	122	343
A/H3/Hong Kong	105	128	168	197
B/Brisbane(Victoria)	62	142	195	254

7. Secondary Outcome

Title	HI Response by Prior Season Vaccination, Yr 1, Day 182 Post Vaccination
Description	Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 182 days post vaccination, 2016-17
Time Frame	Year 1, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients by prior season vaccination status.

Arm/Group Title	IIV-ADJ	IIV-HD	None-ADJ	None-HD
Arm/Group Description	2015-16 Standard dose vaccine recipient who received adjuvanted vaccine in the study in 2016-17	2015-16 Standard dose vaccine recipient who received high dose vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received adjuvanted vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received high dose vaccine in the study in 2016-17
Measure Participants	44	40	14	15
A/H1/California	59	67	48	146
A/H3/Hong Kong	68	84	67	78
B/Brisbane(Victoria)	36	51	86	103

8. Secondary Outcome

Title	HI Response by Prior Season Vaccination, Yr 1, Day 365 Post Vaccination
Description	Hemagglutination inhibition (HI) Titers by prior season (2015-16) vaccination status among adjuvant and high dose vaccine recipients 365 days post vaccination, 2016-17
Time Frame	Year 1, Day 365 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients by prior season vaccination status.

Arm/Group Title	IIV-ADJ	IIV-HD	None-ADJ	None-HD
Arm/Group Description	2015-16 Standard dose vaccine recipient who received adjuvanted vaccine in the study in 2016-17	2015-16 Standard dose vaccine recipient who received high dose vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received adjuvanted vaccine in the study in 2016-17	2015-16 Unvaccinated individual who received high dose vaccine in the study in 2016-17
Measure Participants	44	40	14	15
A/H1/California	51	48	26	73
A/H3/Hong Kong	82	79	58	66
B/Brisbane(Victoria)	20	34	38	44

9. Secondary Outcome

Title	MN Titers, HD vs. AD, Year 1, Day 28 Post Vaccination
Description	Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 28 days post vaccination, 2016-17
Time Frame	Year 1, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients to vaccine and drifted viruses.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H3/Hong Kong 4801 (egg)	256	246
A/H3/Hong Kong 4801 (siat cell)	57	69
A/H3/NZ0783 (siat cell)	47	52
A/H3/OR19 (siat cell)	32	39

10. Secondary Outcome

Title	MN Titers, HD vs. AD, Year 1, Day 182 Post Vaccination
Description	Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 182 days post vaccination, 2016-17
Time Frame	Year 1, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients to vaccine and drifted viruses.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H3/Hong Kong 4801 (egg)	138	132
A/H3/Hong Kong 4801 (siat cell)	44	42
A/H3/NZ0783 (siat cell)	29	30
A/H3/OR19 (siat cell)	24	25

11. Secondary Outcome

Title	MN Titers, HD vs. AD, Year 1, Day 365 Post Vaccination
Description	Microneutralization antibody titers to vaccine and drifted viruses among high dose and adjuvanted vaccine recipients 365 days post vaccination, 2016-17
Time Frame	Year 1, Day 365 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients to vaccine and drifted viruses.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
A/H3/Hong Kong 4801 (egg)	138	132
A/H3/Hong Kong 4801 (siat cell)	45	55
A/H3/NZ0783 (siat cell)	29	30
A/H3/OR19 (siat cell)	24	25

12. Secondary Outcome

Title	MN Titers (A/Hong Kong (Siat Cell)), HD vs. AD, Year 2, Day 28 Post Vaccination
Description	Microneutralization antibody titers to vaccine virus (A/Hong Kong (siat cell) among high dose and adjuvanted vaccine recipients 28 days post vaccination, 2017-18
Time Frame	Year 2, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

Secondary objective examines response in adjuvant and high dose recipients to A/Hong Kong (siat cell) virus in year 2, post vaccination.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study.
Measure Participants	55	58
Geometric Mean (95% Confidence Interval) [Titer]	73	95

13. Secondary Outcome

Title	HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, Year 2, Day 28 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses among adjuvant, high dose and recombinant recipients with prior season standard dose vaccine at 28 days post vaccination 2017-18
Time Frame	Year 2, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

This secondary objective aimed to look at subjects receiving standard dose vaccine in the previous season and one of 3 licensed vaccines in the 2017-18 season.

Arm/Group Title	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+HD	Standard Dose Influenza Vaccine+Recomb
Arm/Group Description	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered a standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants
Measure Participants	20	19	20
A/H1/Michigan	44	86	126
A/H3/Hong Kong	126	163	174
B/Brisbane(Victoria)	35	83	53

14. Secondary Outcome

Title	HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, Year 2, Day 182 Post Vaccination
Description	Hemagglutination Inhibition (HI) titers to vaccine viruses among adjuvant, high dose and recombinant recipients with prior season standard dose vaccine at 182 days post vaccination 2017-18
Time Frame	Year 2, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

This secondary objective aimed to look at subjects receiving standard dose vaccine in the previous season and one of 3 licensed vaccines in the 2017-18 season.

Arm/Group Title	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+HD	Standard Dose Influenza Vaccine+Recomb
Arm/Group Description	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered a standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants
Measure Participants	20	19	20
A/H1/Michigan	26	33	75
A/H3/Hong Kong	95	122	135
B/Brisbane(Victoria)	26	47	33

15. Secondary Outcome

Title	HI Titers, IIV+AD or HD vs. Sequential AD or HD, Year 2, Day 28 Post Vaccination
Description	Hemagglutination inhibition (HI) titers among HD and AD based on prior season vaccination (standard or sequential same vaccination) at 28 days after vaccination, 2017-18
Time Frame	Year 2, Day 28 post vaccination

Outcome Measure Data

Analysis Population Description

This secondary objective selects individuals receiving high dose or adjuvanted vaccine in year 2 of the study and compares immune response by vaccine received in the prior season.

Arm/Group Title	Adjuvant Influenza Vaccine	High Dose Influenza Vaccine	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+HD
Arm/Group Description	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants
Measure Participants	58	55	20	19
A/H1/Michigan	101	83	44	86
A/H3/Hong Kong	158	158	126	163
B/Brisbane(Victoria)	45	63	35	83

16. Secondary Outcome

Title	HI Titers, IIV+AD or HD vs. Sequential AD or HD, Year 2, Day 182 Post Vaccination
Description	Hemagglutination inhibition (HI) titers among HD and AD based on prior season vaccination (standard or sequential same vaccination) at 182 days after vaccination, 2017-18
Time Frame	Year 2, Day 182 post vaccination

Outcome Measure Data

Analysis Population Description

This secondary objective selects individuals receiving high dose or adjuvanted vaccine in year 2 of the study and compares immune response by vaccine received in the prior season.

Arm/Group Title	Adjuvant Influenza Vaccine	High Dose Influenza Vaccine	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+HD
Arm/Group Description	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants
Measure Participants	58	55	20	19
A/H1/Michigan	44	46	26	33
A/H3/Hong Kong	124	101	95	122
B/Brisbane(Victoria)	30	44	26	47

17. Secondary Outcome

Title	Number of Participants With Vaccine Failure, Year 1
Description	Number of Participants with Vaccine Failure in Year 1 by vaccine type
Time Frame	Year 1, Post season

Outcome Measure Data

Analysis Population Description

Results of influenza surveillance after the first year examines individuals by the vaccine type received in Year 1.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine	Standard Dose Influenza Vaccine
Arm/Group Description	This group received High Dose vaccine in the first year of the study.	This group received adjuvanted vaccine in the first year of the study.	This group received standard dose in the first year of the study.
Measure Participants	55	58	59
H3 Positive	4 7.3%	3 5.2%	1 5.3%
B Positive	0 0%	1 1.7%	1 5.3%

18. Secondary Outcome

Title	Number of Participants With Vaccine Failure, Year 2
Description	Number of Participants with Vaccine Failure in Year 2 by two-year vaccine history
Time Frame	Year 2, Post season

Outcome Measure Data

Analysis Population Description

Results of influenza surveillance after the second year examines individuals by groups based on the vaccine types received in both seasons.

Arm/Group Title	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine	Standard+High Dose	Standard+Adjuvanted	Standard+Recombinant
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and high dose influenza vaccination (0.5mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	This group will be administered standard influenza vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants. Recombinant Influenza vaccine: Licensed and FDA approved FluBlok vaccine to be administered to study participants
Measure Participants	55	58	19	20	20
H3 positive	3 5.5%	6 10.3%	1 5.3%	2 10%	3 15%
B positive	4 7.3%	1 1.7%	0 0%	1 5%	1 5%

Adverse Events

Time Frame	18 months of the study
Arm/Group Title	High Dose Influenza Vaccine		Adjuvanted Influenza Vaccine		Standard Dose Influenza Vaccine+HD		Standard Dose Influenza Vaccine +Adj		Standard Dose Influenza Vaccine+Recomb
Arm/Group Description	This group will be administered High Dose (HD) influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants		This group will be administered adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the first and second years of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants		This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year of the study and high dose influenza vaccine (0.5 mL intramuscular (IM) injection) in the second year of the study. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants		This group will be administered standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and adjuvanted influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants		This group will be administered a standard dose flu vaccination (0.5 mL intramuscular (IM) injection) in the first year and recombinant influenza vaccination (0.5 mL intramuscular (IM) injection) in the second year of the study. Standard Dose Influenza vaccine: Licensed and FDA approved Fluvirin vaccine to be administered to study participants Recombinant Influenza vaccine: Licensed and FDA approved FluBlok vaccine to be administered to study participants
All Cause Mortality
	High Dose Influenza Vaccine		Adjuvanted Influenza Vaccine		Standard Dose Influenza Vaccine+HD		Standard Dose Influenza Vaccine +Adj		Standard Dose Influenza Vaccine+Recomb
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/55 (3.6%)		0/58 (0%)		0/19 (0%)		0/20 (0%)		0/20 (0%)
Serious Adverse Events
	High Dose Influenza Vaccine		Adjuvanted Influenza Vaccine		Standard Dose Influenza Vaccine+HD		Standard Dose Influenza Vaccine +Adj		Standard Dose Influenza Vaccine+Recomb
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/58 (0%)		0/19 (0%)		0/20 (0%)		0/20 (0%)
Other (Not Including Serious) Adverse Events
	High Dose Influenza Vaccine		Adjuvanted Influenza Vaccine		Standard Dose Influenza Vaccine+HD		Standard Dose Influenza Vaccine +Adj		Standard Dose Influenza Vaccine+Recomb
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/55 (0%)		0/58 (0%)		0/19 (0%)		0/20 (0%)		0/20 (0%)

Limitations/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.