Open-Label Influenza Vaccine Evaluation (OLIVE)

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)

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.

Study Overview

• Status: Completed
• Conditions: Immune Response
• Intervention / Treatment: Biological: High Dose Influenza vaccine; Biological: Adjuvanted Influenza vaccine; Biological: Standard Dose Influenza vaccine; Biological: Recombinant Influenza vaccine

• Study Type: Interventional
• Enrollment (Actual): 179
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinic - Marshfield Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 65 years to 74 years (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Marshfield Clinic Research Foundation
• Collaborators: Centers for Disease Control and Prevention

Publications and helpful links

General Publications

• McLean HQ, Levine MZ, King JP, Flannery B, Belongia EA. Serologic response to sequential vaccination with enhanced influenza vaccines: Open label randomized trial among adults aged 65-74 years. Vaccine. 2021 Dec 3;39(49):7146-7152. doi: 10.1016/j.vaccine.2021.10.072. Epub 2021 Nov 10.

Study record dates

Study Major Dates

• Study Start: September 1, 2016
• Primary Completion (Actual): April 1, 2018
• Study Completion (Actual): September 1, 2018

Study Registration Dates

• First Submitted: August 16, 2016
• First Submitted That Met QC Criteria: August 16, 2016
• First Posted (Estimate): August 19, 2016

Study Record Updates

• Last Update Posted (Actual): December 19, 2019
• Last Update Submitted That Met QC Criteria: December 3, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; High Dose; Recombinant; Adjuvanted
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: MCL10416

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO