Open-Label Influenza Vaccine Evaluation

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Immune Response

Intervention / Treatment
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* Biological: High Dose Influenza vaccine
* Biological: Adjuvanted Influenza vaccine
* Biological: Standard Dose Influenza vaccine
* Biological: Recombinant Influenza vaccine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 65 Years
Maximum Age: 74 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: High Dose Influenza Vaccine<br>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<br>* Licensed and FDA approved Fluzone HD vaccine to be administered to study participants<br>* Other names: Fluzone HD;|
| Active Comparator: Adjuvanted Influenza Vaccine<br>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<br>* Licensed and FDA approved FluAd vaccine to be administered to study participants<br>* Other names: FluAd;|
| Active Comparator: Standard Dose Influenza Vaccine+HD<br>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<br>* Licensed and FDA approved Fluzone HD vaccine to be administered to study participants<br>* Other names: Fluzone HD;Biological: Standard Dose Influenza vaccine<br>* Licensed and FDA approved Fluvirin vaccine to be administered to study participants<br>* Other names: Fluvirin Standard Dose;|
| Active Comparator: Standard Dose Influenza Vaccine +Adj<br>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<br>* Licensed and FDA approved FluAd vaccine to be administered to study participants<br>* Other names: FluAd;Biological: Standard Dose Influenza vaccine<br>* Licensed and FDA approved Fluvirin vaccine to be administered to study participants<br>* Other names: Fluvirin Standard Dose;|
| Active Comparator: Standard Dose Influenza Vaccine+Recomb<br>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<br>* Licensed and FDA approved Fluvirin vaccine to be administered to study participants<br>* Other names: Fluvirin Standard Dose;Biological: Recombinant Influenza vaccine<br>* Licensed and FDA approved FluBlok vaccine to be administered to study participants<br>* Other names: FluBlok;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Titers, HD vs. AD, Yr 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 | Year 1, Day 28 post vaccination | 
| HI Titers, HD vs. AD, Yr 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 | Year 1, Day 182 post vaccination | 
| HI Titers, HD vs. AD, Yr 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 | Year 1, Day 365 post vaccination | 
| HI Titers, HD vs. AD, Yr 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 | Year 2, Day 28 post vaccination | 
| HI Titers, HD vs. AD, Yr 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 | Year 2, Day 182 post vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HI Response by Prior Season Vaccination, Yr 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 | Year 1, Day 28 post vaccination | 
| HI Response by Prior Season Vaccination, Yr 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 | Year 1, Day 182 post vaccination | 
| HI Response by Prior Season Vaccination, Yr 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 | Year 1, Day 365 post vaccination | 
| MN Titers, HD vs. AD, 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 | Year 1, Day 28 post vaccination | 
| MN Titers, HD vs. AD, 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 | Year 1, Day 182 post vaccination | 
| MN Titers, HD vs. AD, 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 | Year 1, Day 365 post vaccination | 
| MN Titers (A/Hong Kong (Siat Cell)), HD vs. AD, 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 | Year 2, Day 28 post vaccination | 
| HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, 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 | Year 2, Day 28 post vaccination | 
| HI Titers, HD vs. AD vs. RIV With Prior Season Standard (IIV) Dose, 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 | Year 2, Day 182 post vaccination | 
| HI Titers, IIV+AD or HD vs. Sequential AD or HD, 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 | Year 2, Day 28 post vaccination | 
| HI Titers, IIV+AD or HD vs. Sequential AD or HD, 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 | Year 2, Day 182 post vaccination | 
| Number of Participants With Vaccine Failure, Year 1 | Number of Participants with Vaccine Failure in Year 1 by vaccine type | Year 1, Post season | 
| Number of Participants With Vaccine Failure, Year 2 | Number of Participants with Vaccine Failure in Year 2 by two-year vaccine history | Year 2, Post season | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vaccine, Influenza, High Dose, Adjuvanted, Recombinant