High-Dose Vaccine for Flu

No longer recruiting at 21 trial locations

Overseen By Trial Transparency email recommended (Toll free for US & Canada)

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: Sanofi Pasteur, a Sanofi Company

Must not be taking: Immunosuppressants, Anticoagulants

Disqualifiers: Immunodeficiency, Guillain-Barré, Bleeding disorder, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a high-dose flu vaccine to evaluate its effectiveness and safety for adults aged 50 to 64. Participants will receive a single injection of either the high-dose vaccine or a standard-dose vaccine for comparison. This trial suits adults in the specified age range who have not received a flu shot in the past six months and are not currently experiencing any serious health issues. The study aims to determine if the higher dose provides better protection against the flu. As a Phase 3 trial, it represents the final step before FDA approval, offering participants the opportunity to contribute to important research that could lead to a new, more effective flu vaccine.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, long-term systemic corticosteroids, or anticoagulants, you may not be eligible to participate.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive therapy, long-term corticosteroids, or anticoagulants, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the high-dose trivalent flu vaccine, such as Fluzone High-Dose, has undergone safety testing. Some studies found it might cause more side effects than the regular flu shot, typically mild ones like soreness at the injection site or a slight fever. However, the high-dose version offers better flu protection, particularly for older adults.

Although some discomfort may occur after receiving the shot, the vaccine is generally well-tolerated. The FDA has approved it for individuals 65 and older, indicating it meets specific safety standards. This approval suggests it is also safe for other age groups, including those in this study, which focuses on adults aged 50 to 64. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the high-dose trivalent influenza vaccine (IIV-HD) because it offers a stronger immune response compared to standard flu vaccines, especially for vulnerable populations like older adults. Unlike typical seasonal flu vaccines that use standard doses, IIV-HD contains a higher dose of antigen, which is the component that triggers the body's immune defense. This enhanced formula aims to provide better protection against the flu by boosting the body's ability to fight off the virus more effectively. Additionally, this approach could lead to fewer cases of severe flu and related complications, making it a promising advancement in flu prevention.

What evidence suggests that this trial's treatments could be effective for flu?

This trial will compare the high-dose trivalent flu vaccine (IIV-HD) with the standard-dose flu vaccine (IIV-SD). Studies have shown that the high-dose trivalent flu vaccine offers 24% better protection against flu infections than the regular flu shot. Large studies with older adults have proven this effectiveness. The vaccine enhances the immune system's ability to produce more antibodies, which are proteins that combat the flu virus. These findings suggest that the high-dose vaccine could offer stronger protection against the flu for adults. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults aged 50 to 64 who are in good health and can commit to the study schedule. Women must either be postmenopausal, surgically sterile, or willing to use effective contraception. Participants need a negative pregnancy test if applicable and must provide informed consent.

Inclusion Criteria

I am between 50 and 64 years old.

I agree to use effective birth control or abstain from sex during the study period.

I am not able to have children because I am postmenopausal or have been surgically sterilized.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intramuscular injection of either IIV-HD or IIV-SD on Day 1

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including measurement of antibody titers and adverse events

180 days

What Are the Treatments Tested in This Trial?

Interventions

• High-Dose trivalent influenza vaccine

Trial Overview The study compares two flu vaccines: a high-dose version versus a standard-dose one. It aims to assess how well these vaccines work (immunogenicity) and their safety in adults aged 50 through 64.

How Is the Trial Designed?

Group I: IIV-HD Experimental Treatment 1 Intervention

Participants will receive a single intramuscular (IM) injection of IIV-HD at Day 1

Group II: IIV-SD Active Control 1 Intervention

Participants will receive a single intramuscular (IM) injection of IIV-SD at Day 1

High-Dose trivalent influenza vaccine is already approved in United States, European Union for the following indications:

Approved in United States as Fluzone High-Dose for:

• Influenza prevention in adults 65 years and older
• Influenza prevention in adults 18 through 64 years who have had a solid organ transplant and are taking immunosuppressive medications

Approved in European Union as Fluzone High-Dose Trivalent for:

• Influenza prevention in adults 65 years and older

Who Is Running the Clinical Trial?

Sanofi Pasteur, a Sanofi Company

Lead Sponsor

Trials

429

Recruited

6,140,000+

Paul Hudson

Sanofi Pasteur, a Sanofi Company

Chief Executive Officer since 2019

Degree in Economics from Manchester Metropolitan University

Dr. Thomas Triomphe

Sanofi Pasteur, a Sanofi Company

Chief Medical Officer since 2020

MD from Tehran University of Medical Sciences

Published Research Related to This Trial

High dose trivalent influenza vaccine (TIV) significantly reduces the incidence of laboratory-confirmed influenza, particularly the A(H3N2) strain, in older adults, with a relative risk of 0.76 based on a meta-analysis of 16 trials involving 47,857 patients.

The high dose TIV was associated with a stronger immune response and fewer serious adverse events compared to the standard dose, indicating it is a safer and more effective option for preventing influenza in older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of high dose trivalent influenza vaccine in adults and immunosuppressed populations - A systematic review and meta-analysis. Leibovici Weissman, Y., Cooper, L., Sternbach, N., et al.[2021]

The study involving 661 children aged 6 months to under 18 years demonstrated that the high-dose quadrivalent influenza vaccine (IIV4-HD) is safe, with no serious adverse events reported and similar rates of mild reactions compared to the standard-dose vaccine.

IIV4-HD at a dose of 60 µg significantly improved immune responses, particularly in younger children (6 months to <3 years), showing higher antibody titers against various influenza strains compared to the standard-dose vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through Chang, LJ., Anderson, EJ., Jeanfreau, R., et al.[2021]

Fluzone High-Dose is an injectable influenza vaccine specifically designed for individuals aged 65 and older, containing a higher amount of hemagglutinin antigen to improve immune response compared to standard vaccines.

The FDA approved Fluzone High-Dose for this age group due to their increased risk of severe influenza outcomes, although the Advisory Committee on Immunization Practices did not express a preference for it over other vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Licensure of a high-dose inactivated influenza vaccine for persons aged >or=65 years (Fluzone High-Dose) and guidance for use - United States, 2010. [2017]

Fluzone® High-Dose (IIV3-HD) vaccine, designed for adults aged 65 and older, has been shown to produce significantly stronger antibody responses and better protection against influenza compared to standard-dose vaccines, based on multiple studies since 2004.

IIV3-HD is considered a cost-effective option for older adults, potentially even saving costs compared to standard-dose vaccines, and further research is suggested to explore its benefits for individuals with weakened immune systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fluzone® High-Dose Influenza Vaccine. Robertson, CA., DiazGranados, CA., Decker, MD., et al.[2018]

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]

In a study involving 2670 healthy adults aged 65 and older, the quadrivalent high-dose influenza vaccine (IIV4-HD) demonstrated non-inferior immunogenicity compared to the licensed trivalent high-dose vaccine (IIV3-HD) for all four influenza strains.

IIV4-HD showed superior immune responses for both B strains compared to IIV3-HD that did not contain the same B-lineage strain, while maintaining a similar safety profile, indicating it is a more effective option without added safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high-dose quadrivalent influenza vaccine in adults ≥65 years of age: A phase 3 randomized clinical trial. Chang, LJ., Meng, Y., Janosczyk, H., et al.[2020]

Citations

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

Fluzone High-Dose Seasonal Influenza Vaccine A randomized efficacy study published in the New England Journal of Medicine indicated that the trivalent high-dose vaccine was 24% more ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6422785/

High-dose influenza vaccination - PMC A cohort study including 2 722 909 adults aged 65 years and older found that HD-TIV was associated with a 36% (95% CI 9% to 56%) reduction in post-influenza ...

3. sanofiflushots.com sanofiflushots.com/see-the-studies

Sanofi Vaccines Safety & Efficacy Studies Higher dose provides higher protection: With 4x the dose, Fluzone ® High-Dose provides 24% better protection compared to a regular flu shot. Syringe icon. Study ...

4. pro.campus.sanofi pro.campus.sanofi/us/products/sanofiflu/fluzone-high-dose-influenza-vaccine

Fluzone® High-Dose (Influenza Vaccine) for 65+ | Sanofiflu In an RCT conducted in 2011-2012 and 2012-2013 in approximately 32,000 adults 65+, Fluzone High-Dose was 24% (95% CI: 10, 37) more effective (rVE) against ...

5. fda.gov fda.gov/media/139731/download

Package Insert - Fluzone High-Dose Fluzone High-Dose stimulates the immune system to produce antibodies that help protect against influenza. Instruct that annual influenza vaccination is ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4310469/

Safety of high dose trivalent inactivated influenza vaccine in ... Recently, a high dose (HD) TIV was found to increase the level of antibody response in elderly patients compared to the standard dose (SD) TIV. We hypothesized ...