Flu Vaccine Effectiveness in Aging

(FluVax3 Trial)

Overseen By George Kuchel, MD, FRCP

Age: 65+

Sex: Any

Trial Phase: Phase 4

Sponsor: The Jackson Laboratory

Must not be taking: High-dose corticosteroids

Disqualifiers: Cancer, Heart disease, COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 19

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand why older adults sometimes respond less effectively to the flu vaccine. Participants will receive three different FDA-approved flu vaccines over three years, while researchers collect blood, nasal, and stool samples to study changes. The trial focuses on how the body reacts to the vaccines over time, not on safety. Individuals who are 65 or older, healthy, and willing to receive flu shots over three years might be suitable candidates. However, those with certain health conditions, such as asthma, heart disease, or severe allergies to vaccine components, should not participate. As a Phase 4 trial, the vaccines are already FDA-approved and proven effective, and this research aims to understand how they benefit more patients.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, if you are taking medicines that alter immune response, like high-dose corticosteroids, you may not be eligible to participate.

What is the safety track record for these flu vaccines?

Research shows that the flu vaccines used in this study are safe for older adults. Fluzone High-Dose, one of the vaccines, proves more effective at preventing the flu in people aged 65 and older compared to regular flu shots. Its FDA approval for this age group indicates thorough safety testing and good tolerance.

Another vaccine in the study, FLUAD, also demonstrates greater effectiveness at preventing confirmed flu cases in older adults, suggesting its likely safety for this group. Since the FDA has approved these vaccines for older adults, any side effects are usually mild and temporary, such as soreness at the injection site or a mild fever. Overall, these vaccines are considered safe for older adults. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about the flu vaccines under study because they are specifically tailored for healthy older adults, a group that can be more vulnerable to the flu. Unlike standard flu vaccines that may be used across all age groups, these vaccines include formulations like Fluzone HD, FLUAD, and Flublok Quadrivalent, which are enhanced to provide a stronger immune response. This approach aims to improve the effectiveness of flu prevention in older adults, potentially leading to better protection against the flu and fewer complications for this age group.

What is the effectiveness track record for the flu vaccine in older adults?

Research has shown that high-dose flu vaccines work better for older adults than regular-dose vaccines. One study found that high-dose vaccines offered better protection against the flu for people aged 65 and older. Another study demonstrated that these vaccines improved the immune response in older adults, enhancing their effectiveness. Specifically, a higher-dose flu vaccine made with recombinant technology was linked to 15% fewer flu cases in older patients. In this trial, healthy older adults will receive FDA-approved influenza vaccines, including Fluzone HD in Year 1, FLUAD in Year 2, and Flublok Quadrivalent in Year 3. These vaccines have already been approved and have proven effective in reducing flu cases in older populations. ^{3 6 7 8 9}

Who Is on the Research Team?

George Kuchel, MD, FRCP

Principal Investigator

UConn Center on Aging

Are You a Good Fit for This Trial?

This trial is for English-speaking men and women aged 65 or older, weighing at least 110 lbs, who are willing to participate in a three-year study involving 19 visits. Participants must be open to receiving annual flu vaccines and providing blood samples. They should not have severe reactions to past flu vaccines but cannot join if they've had Guillain-Barre syndrome after vaccination, recent other vaccinations, egg allergies, certain chronic diseases, or conditions affecting the immune system.

Inclusion Criteria

Able to speak and read English

I agree not to get any vaccines 2 weeks before and after my flu shots for the next three flu seasons.

I am 65 years old or older as of September 1, 2022.

Exclusion Criteria

You are allergic to eggs or any ingredient in the flu vaccine.

I have not received any vaccines within 2 weeks before my flu shot for the 2022-25 seasons.

I have received the flu vaccine for the 2022-23 season.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination Year 1

Participants receive the Fluzone Quadrivalent High-Dose vaccine and undergo blood sampling for antibody and immune cell analysis

6 months

6 visits (in-person)

Vaccination Year 2

Participants receive the FLUAD Quadrivalent vaccine and undergo blood sampling for antibody and immune cell analysis

6 months

6 visits (in-person)

Vaccination Year 3

Participants receive the Flublok Quadrivalent vaccine and undergo blood sampling for antibody and immune cell analysis

6 months

6 visits (in-person)

Follow-up

Participants are monitored for immune response and effectiveness after each vaccination year

6 months

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Flu Vaccine (Year 1)
• Flu Vaccine (Year 2)
• Flu Vaccine (Year 3)

Trial Overview The study aims to understand why older adults may have a reduced response to influenza vaccines by administering different flu shots over three years. It involves regular collection of blood samples as well as nasal swabs and stool samples at specific times during the study period.

How Is the Trial Designed?

Group I: Healthy Older Adults Experimental Treatment 3 Interventions

Will receive FDA-approved influenza vaccine (Fluzone HD Year 1, FLUAD Year 2, Flublok Quadrivalent Year 3)

Flu Vaccine (Year 1) is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Fluzone High-Dose for:

• Prevention of influenza A and B in individuals 65 years and older

Approved in European Union as Fluad for:

• Prevention of influenza A and B in adults 65 years and older

Approved in Canada as Fluvirin for:

• Prevention of influenza A and B in individuals 6 months and older, including those 65 years and older

Approved in Japan as Fluarix Tetra for:

• Prevention of influenza A and B in individuals 6 months and older, including those 65 years and older

Who Is Running the Clinical Trial?

The Jackson Laboratory

Lead Sponsor

Trials

6

Recruited

2,200+

University of Chicago

Collaborator

Trials

1,086

Recruited

844,000+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

UConn Health

Collaborator

Trials

218

Recruited

59,100+

Icahn School of Medicine at Mount Sinai

Collaborator

Trials

933

Recruited

579,000+

Weill Medical College of Cornell University

Collaborator

Trials

1,103

Recruited

1,157,000+

Published Research Related to This Trial

In a study of 59 patients with hypothyroidism, combination therapy using T(3) and T(4) showed significant improvements in quality of life and depression scores compared to T(4) monotherapy, with 49% of participants preferring the combination therapy.

The study maintained stable serum TSH levels across both treatment groups, indicating that the combination therapy was effective without disrupting thyroid hormone balance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of combination therapy with thyroxine (T4) and 3,5,3'-triiodothyronine versus T4 monotherapy in patients with hypothyroidism, a double-blind, randomised cross-over study. Nygaard, B., Jensen, EW., Kvetny, J., et al.[2022]

Recent studies indicate that while levothyroxine (L-T4) is the standard treatment for hypothyroidism, some patients may benefit from adding triiodothyronine (T3) due to genetic factors affecting thyroid hormone activation.

Specifically, a polymorphism in the D2 gene (Thr92Ala) may lead to reduced conversion of T4 to T3, which could explain persistent fatigue in patients on L-T4 alone, suggesting that T3 could be considered for a trial in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination L-T3 and L-T4 therapy for hypothyroidism. Wartofsky, L.[2013]

In a study of 233 patients with lumbar foraminal stenosis (LFS), selective nerve root block (SNRB) significantly reduced pain by 51% after just 2 weeks, indicating its efficacy as a treatment option.

Patients with lower grades of LFS (1T, 2, 3) experienced greater and more sustained symptomatic improvement compared to those with grade IV LFS, highlighting the importance of stenosis severity in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Pain-reducing Effect After Selective Nerve Root Block According to the Type of Lumbar Foraminal Stenosis. Ko, S., Kwon, J., Lee, Y., et al.[2020]

The incidence of differentiated thyroid cancer is rising globally, especially among older patients who tend to have more aggressive forms of the disease and higher mortality rates.

A risk-benefit analytic approach is recommended for treating thyroid cancer in older individuals, focusing on individual patient factors and balancing treatment effectiveness with potential side effects to optimize care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimal differentiated thyroid cancer management in the elderly. McLeod, DS., Carruthers, K., Kevat, DA.[2018]

Stage III lung cancer, which includes both IIIa and IIIb, accounts for about one third of all non-small-cell lung cancer cases, with 40,000 to 50,000 new diagnoses each year.

Current treatment strategies for stage III lung cancer involve surgery combined with chemotherapy and/or radiation for stage IIIa, while stage IIIb primarily relies on chemoradiation, with ongoing clinical trials exploring targeted therapies and improved radiation techniques to reduce tumor failures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined modality therapy for stage III non-small-cell lung cancer. Anderson, CS., Curran, WJ.[2010]

In a Phase III study involving 234 patients with Stage III non-small-cell lung cancer, neither split-course b.i.d. radiotherapy nor standard q.d. radiotherapy showed superior survival outcomes, with median overall survival rates of 14 months for q.d. and 15 months for b.i.d.

The incidence of severe acute toxicities was similar between the two treatment arms, indicating that both treatment regimens had comparable safety profiles, with no significant differences in time to progression or local failure rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase III trial comparing chemotherapy plus once-daily or twice-daily radiotherapy in Stage III non-small-cell lung cancer. Schild, SE., Stella, PJ., Geyer, SM., et al.[2019]

During the 2014/15 flu season, the effectiveness of the influenza vaccine against the A(H3N2) strain was relatively low, with an overall effectiveness of only 33%.

For individuals aged 65 and older, the vaccine showed a slightly better effectiveness of 40%, and it was found to reduce the likelihood of hospital admissions due to influenza by 44%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results. Puig-Barbera, J., Mira-Iglesias, A., Tortajada-Girbes, M., et al.[2019]

A comprehensive analysis of 36 trials involving 7532 adults aged 65 and older showed that the MF59-adjuvanted trivalent influenza vaccine (aIIV3) has a similar safety profile to the nonadjuvanted vaccine (IIV3), with comparable rates of adverse events (24.8% for aIIV3 vs 26.7% for IIV3).

The study found no significant differences in serious adverse events or other safety concerns between the two vaccines, indicating that aIIV3 is a safe option for older adults receiving influenza vaccination.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cumulative clinical experience with MF59-adjuvanted trivalent seasonal influenza vaccine in young children and adults 65 years of age and older. Lindert, K., Leav, B., Heijnen, E., et al.[2019]

In a study involving 757 adults aged 65 and older, the safety profile of the trivalent adjuvanted inactivated influenza vaccine (aIIV3) was found to be noninferior to that of the trivalent high-dose inactivated influenza vaccine (HD-IIV3), with similar rates of moderate-to-severe injection-site pain and other reactions.

Both vaccines did not show significant differences in health-related quality of life (HRQOL) changes post-vaccination, indicating that either vaccine is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Schmader, KE., Liu, CK., Harrington, T., et al.[2021]

The MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) showed consistent effectiveness over standard egg-based quadrivalent vaccines (IIV4e) in preventing influenza-related medical encounters among adults aged 65 and older during the 2017-2020 influenza seasons.

When compared to the high-dose influenza vaccine (HD-IIV3), aIIV3 provided better overall benefits while showing comparable effectiveness in at-risk populations, indicating its potential as a superior option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine over Three Consecutive Influenza Seasons in the United States. Boikos, C., McGovern, I., Ortiz, JR., et al.[2022]

Fluzone® High Dose, approved by the FDA for individuals 65 and older, contains four times more hemagglutinin than standard vaccines, leading to a stronger immune response against influenza.

A recent randomized controlled trial showed that this high-dose vaccine maintains a favorable safety profile while enhancing immunologic response, supporting its use in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the vaccination of the elderly against influenza: role of a high-dose vaccine. Sullivan, SJ., Jacobson, R., Poland, GA.[2010]

A study of 1,553 patients with stage III melanoma found that their 5-year melanoma-specific survival (MSS) rates were lower than those reported in the American Joint Committee on Cancer (AJCCv8) guidelines, indicating a need for improved treatment strategies.

Specifically, the MSS rates for stage IIIA and IIIB patients were significantly less favorable in the Central Malignant Melanoma Registry cohort compared to AJCCv8, highlighting the ongoing challenges in managing these melanoma stages despite recent therapy advancements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognosis of Patients With Stage III Melanoma According to American Joint Committee on Cancer Version 8: A Reassessment on the Basis of 3 Independent Stage III Melanoma Cohorts. Garbe, C., Keim, U., Suciu, S., et al.[2021]

A joint conference by major thyroid associations concluded that there is still uncertainty about the benefits of combining levothyroxine (LT4) and liothyronine (LT3) for thyroid treatment, despite 14 clinical trials showing inconsistent results.

Consensus statements were developed to guide future clinical trials, emphasizing the need for studies to include patients dissatisfied with current therapy, utilize patient-reported outcomes, and ensure robust trial designs to better assess the efficacy of combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-Based Use of Levothyroxine/Liothyronine Combinations in Treating Hypothyroidism: A Consensus Document. Jonklaas, J., Bianco, AC., Cappola, AR., et al.[2022]

In a systematic review of 7 randomized controlled trials involving 348 hypothyroid patients, about 46.2% preferred the combination of L-T3 and L-T4 over L-T4 alone, indicating a significant level of interest in combination therapy, though this preference was not statistically significant compared to chance.

The preference for combination therapy was partially linked to improvements in thyroid-stimulating hormone (TSH) levels, mood, and symptoms, suggesting that these factors may influence patient satisfaction with treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review and Meta-Analysis of Patient Preferences for Combination Thyroid Hormone Treatment for Hypothyroidism. Akirov, A., Fazelzad, R., Ezzat, S., et al.[2020]

In a study involving over 3.8 million older adults with health conditions during the 2017-2019 influenza seasons, the MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) was found to be significantly more effective than the standard quadrivalent inactivated influenza vaccine (IIV4) in preventing influenza-related medical encounters, with a relative vaccine effectiveness increase of 7.1% in 2017-2018 and 20.4% in 2018-2019.

The high-dose trivalent inactivated influenza vaccine (HD-IIV3) showed comparable effectiveness to aIIV3, indicating that both enhanced vaccines provide better protection for older adults who are at higher risk for influenza complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of the Adjuvanted Influenza Vaccine in Older Adults at High Risk of Influenza Complications. Boikos, C., Imran, M., Nguyen, VH., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10276206/

High-dose influenza vaccine in older adults by age and ... Subgroup analyses showed HD-IIV consistently provided better protection than SD-IIV against influenza outcomes across the age range (65+, 75+ 85+ years), and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1201971225002073

Comparable effectiveness of MF59®-adjuvanted and high- ... High-dose influenza vaccines increase the magnitude of the immune response in older adults and have been proven to be more effective than standard-dose vaccines ...

3. cdc.gov cdc.gov/acip/grade/influenza-older-adults.html

GRADE: Higher Dose and Adjuvanted Influenza Vaccines ... Comparative effectiveness of high-dose versus standard-dose influenza vaccines in US residents aged 65 years and older from 2012 to 2013 using ...

4. divisionofresearch.kaiserpermanente.org divisionofresearch.kaiserpermanente.org/flublok-vaccine-comparison/

Flublok vaccine improved protection from flu for older adults A higher-dose flu vaccine using recombinant technology was associated with 15% fewer flu cases in older patients than the commonly used, standard-dose flu ...

5. cslseqirus.us cslseqirus.us/news/seqirus-presents-new-data-at-eswi-8th-virtual-conference

New Data Supports the Effectiveness of Adjuvanted ... Results suggest that vaccination with aQIV in older adults helped prevent 4,141 symptomatic influenza cases, 759 office visits, 441 ...

6. cdc.gov cdc.gov/flu/vaccine-types/flu-zone.html

Fluzone High-Dose Seasonal Influenza Vaccine ... high-dose vaccine was 24% more effective in preventing flu in adults 65 years and older relative to a standard-dose vaccine. Both Fluzone High- ...

7. fda.gov fda.gov/media/132238/download

Package Insert - Fluzone High-Dose Quadrivalent Safety, immunogenicity, and efficacy of Fluzone High-Dose Quadrivalent have been evaluated in adults 65 years of age and older [see Adverse Reactions (6.1) and ...

8. doh.wa.gov doh.wa.gov/sites/default/files/legacy/Documents/Pubs//348-518-SupplementalGuidance.pdf

High-Dose and Adjuvanted Flu Vaccine for Persons 65 ... FLUAD™ was significantly more effective at preventing lab-confirmed influenza infection in older adults compared to a trivalent vaccine without an adjuvant.

9. cdc.gov cdc.gov/flu/highrisk/65over.htm

Flu and People 65 Years and Older | Influenza (Flu) People 65 years and older are at higher risk of developing serious flu complications compared with young, healthy adults.