Open-Label Influenza Vaccine Evaluation

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)

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02872311

Acronym

OLIVE

Enrollment

179

Registered

2016-08-19

Start date

2016-09-30

Completion date

2018-09-30

Last updated

2025-12-10

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Immune Response

Keywords

Vaccine, Influenza, High Dose, Adjuvanted, Recombinant

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.

Interventions

BIOLOGICALHigh Dose Influenza vaccine

Licensed and FDA approved Fluzone HD vaccine to be administered to study participants

BIOLOGICALAdjuvanted Influenza vaccine

Licensed and FDA approved FluAd vaccine to be administered to study participants

BIOLOGICALStandard Dose Influenza vaccine

Licensed and FDA approved Fluvirin vaccine to be administered to study participants

BIOLOGICALRecombinant Influenza vaccine

Licensed and FDA approved FluBlok vaccine to be administered to study participants

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

65 Years to 74 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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
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
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
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
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

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

Countries

United States

Participant flow

Participants by arm

Arm	Count
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. High Dose Influenza vaccine: Licensed and FDA approved Fluzone HD vaccine to be administered to study participants	55
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. Adjuvanted Influenza vaccine: Licensed and FDA approved FluAd vaccine to be administered to study participants	58
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. 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	19
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. 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	20
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. 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	20
Total	172

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Death	2	0	0
Overall Study	Lost to Follow-up	2	0	0
Overall Study	Protocol Violation	0	2	1

Baseline characteristics

Characteristic	High Dose Influenza Vaccine	Adjuvanted Influenza Vaccine	Standard Dose Influenza Vaccine+HD	Standard Dose Influenza Vaccine +Adj	Standard Dose Influenza Vaccine+Recomb	Total
Age, Continuous	70 years STANDARD_DEVIATION 2.7	69.6 years STANDARD_DEVIATION 2.6	69.4 years STANDARD_DEVIATION 2.9	69.2 years STANDARD_DEVIATION 2.2	70 years STANDARD_DEVIATION 2.7	70 years STANDARD_DEVIATION 2.6
Race/Ethnicity, Customized Race : White	55 Participants	58 Participants	19 Participants	20 Participants	20 Participants	172 Participants
Region of Enrollment United States	55 Participants	58 Participants	19 Participants	20 Participants	20 Participants	172 Participants
Sex: Female, Male Female	26 Participants	33 Participants	10 Participants	12 Participants	9 Participants	90 Participants
Sex: Female, Male Male	29 Participants	25 Participants	9 Participants	8 Participants	11 Participants	82 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	2 / 55	0 / 58	0 / 19	0 / 20	0 / 20
other Total, other adverse events	0 / 55	0 / 58	0 / 19	0 / 20	0 / 20
serious Total, serious adverse events	0 / 55	0 / 58	0 / 19	0 / 20	0 / 20

Outcome results

Primary

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

Time frame: Year 1, Day 182 post vaccination