Flu Vaccines for Influenza

No longer recruiting at 7 trial locations

Overseen By Richard Zimmerman, MD,MPH

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: Duke University

Must not be taking: Live vaccines, Non-live vaccines

Disqualifiers: Pregnancy, Guillain-Barré syndrome, 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: 5

Duration: 4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests different flu vaccines to determine which provides the best immune response and longest-lasting protection. Participants will receive either Flucelvax or another licensed flu vaccine, such as Flublok or Fluzone. The study involves providing blood samples and completing weekly health surveys to monitor any flu-like symptoms. It seeks adults who have not yet received a flu shot this season and are willing to communicate via email or text messages. As a Phase 4 trial, this research aims to understand how these FDA-approved and effective vaccines benefit more patients.

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

The trial information does not specify whether you need to stop taking your current medications. However, it does mention that you should not receive any live vaccines within 6 weeks or non-live vaccines within 2 weeks before joining the study.

What is the safety track record for these treatments?

Research shows that the three vaccines in this trial—Flublok, Fluzone, and Flucelvax—are generally safe and well-tolerated. Studies have found that Flublok poses no higher risk of negative effects in pregnant individuals compared to regular flu vaccines, indicating it is well-tolerated across different groups. Fluzone, widely used and free of live virus, cannot cause the flu, though some may experience mild side effects like soreness at the injection site. In studies, serious side effects from Flucelvax occurred in less than 1% of participants, supporting its safety. Overall, the FDA has approved these vaccines, confirming they have passed strict safety tests. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these flu vaccines because they offer unique production methods and potential benefits. Flublok is made using recombinant DNA technology, which means it doesn't use the influenza virus or eggs, making it a great option for people with egg allergies. Flucelvax is cultured in animal cells, which may result in fewer mutations and better match the circulating virus strains. These differences could lead to improved effectiveness and wider accessibility compared to traditional egg-based flu vaccines.

What is the effectiveness track record for these flu vaccines?

Research shows that the vaccines Flublok, Fluzone, and Flucelvax effectively prevent the flu. In this trial, participants will receive either Flublok or Fluzone in one group, or Flucelvax in another. Studies indicate that Flublok, made using a special process, may offer better protection than regular flu shots, particularly against influenza A. Fluzone, especially in its high-dose version, is 24% more effective for older adults than standard flu vaccines. Flucelvax, produced using cells, significantly reduces flu cases in children compared to vaccines that don't target the flu. Overall, these vaccines strengthen the immune system and lower the risk of contracting the flu. ^{6 7 8 9 10}

Who Is on the Research Team?

Emmanuel B Walter, MD, MPH

Principal Investigator

Duke University

Are You a Good Fit for This Trial?

This trial is for individuals who want to help test the effectiveness of different flu vaccines: Flucelvax, Flublok, or Fluzone. Participants should be willing to provide blood and saliva samples over several months and report any symptoms of influenza-like illness.

Inclusion Criteria

Willing to provide written/electronic informed consent

I plan to get the flu vaccine as recommended.

I can commit to the full study period and attend all required follow-ups.

Exclusion Criteria

Any condition which, in the opinion of the investigators, may pose a health risk to the participant or interfere with the evaluation of the study objectives

I have had Guillain-Barré syndrome in the past.

I haven't had live vaccines in 6 weeks or non-live vaccines in 2 weeks before joining this study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an influenza vaccine (Flucelvax, Flublok, or Fluzone) and provide blood samples for biomarker measurement

4 weeks

3 visits (in-person)

Follow-up

Participants are monitored for immune response and influenza-like illness symptoms, with weekly electronic surveys and potential additional blood draws

24 weeks

Weekly electronic surveys, up to 2 additional blood draws if symptomatic

What Are the Treatments Tested in This Trial?

Interventions

• Flublok
• Flucelvax
• Fluzone

Trial Overview The study compares three approved flu vaccines by measuring immune responses in participants. It involves random assignment to one vaccine type, regular health surveys, and collection of blood/saliva at specific times to assess immunogenicity.

How Is the Trial Designed?

Group I: Flucelvax (ccIIV4) Experimental Treatment 1 Intervention

Participants will receive Flucelvax (ccIIV4) at Visit 1.

Group II: Flublok (RIV) or Fluzone (IIV) Experimental Treatment 1 Intervention

Participants will receive Flublok (RIV) or Fluzone (IIV) at Visit 1.

Who Is Running the Clinical Trial?

Duke University

Lead Sponsor

Trials

2,495

Recruited

5,912,000+

VA Medical Center-Cleveland

Collaborator

Trials

1

Recruited

610+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Arizona State University

Collaborator

Trials

311

Recruited

109,000+

VA Northeast Ohio Health Care

Collaborator

Trials

2

Recruited

1,100+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

University Hospitals Cleveland Medical Center

Collaborator

Trials

348

Recruited

394,000+

Published Research Related to This Trial

The high-dose inactivated influenza vaccine quadrivalent (HD-IIV4) has been shown to be safe and effective in preventing influenza in adults aged 65 and older, with improved immunogenicity against additional B strains compared to standard vaccines.

Despite some increased adverse reactions like injection-site pain and myalgia, HD-IIV4 is recommended as the vaccine of choice for older adults due to its superior efficacy compared to other influenza vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Inactivated Influenza Vaccine Quadrivalent for Older Adults. Chahine, EB.[2021]

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]

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]

A new active surveillance system called SICOVA was developed in Mexico to monitor adverse events (AEs) following quadrivalent influenza vaccination, involving 2013 participants over three influenza seasons.

The overall adverse event rate was 9.09%, with most AEs being mild and not requiring medical visits, confirming the established safety profile of the Fluzone® Quadrivalent vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved post-marketing safety surveillance of quadrivalent inactivated influenza vaccine in Mexico using a computerized, SMS-based follow-up system. Betancourt-Cravioto, M., Cervantes-Powell, P., Tapia-Conyer, R., et al.[2022]

In a study involving 741 healthcare workers, the cell-based quadrivalent vaccine Flucelvax Tetra was found to have a high safety profile, with 99.8% of reported adverse events classified as not serious.

Out of 430 adverse events following immunization, only one was serious, and causality assessment indicated it was not linked to the vaccine, suggesting that Flucelvax Tetra is safe for use in healthcare settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-Marketing Active Surveillance of Adverse Reactions Following Influenza Cell-Based Quadrivalent Vaccine: An Italian Prospective Observational Study. Stefanizzi, P., De Nitto, S., Spinelli, G., et al.[2021]

The recombinant hemagglutinin quadrivalent influenza vaccine (RIV4) was approved for use in individuals 18 years and older, showing a safety profile similar to standard-dose vaccines, with 95% of reported adverse events being non-serious.

Among the serious adverse events reported, there were 10 cases of Guillain-Barré syndrome, highlighting the importance of ongoing safety monitoring, although the overall incidence of serious reactions appears low.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of quadrivalent recombinant influenza vaccine: Reports to the vaccine adverse event reporting system. Woo, EJ., Moro, PL.[2021]

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 pilot study involving 385 children and adolescents, the most common adverse event following the Fluenz Tetra nasal vaccine was nasal congestion, reported by 43.4% of participants, indicating that while side effects occurred, they were generally mild.

No serious adverse events or hospitalizations were reported, suggesting that the Fluenz Tetra vaccine is safe for use in children, with no significant safety concerns identified during the 2014/2015 influenza season.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Intranasal Quadrivalent Live Attenuated Influenza Vaccine (QLAIV) in Children and Adolescents: A Pilot Prospective Cohort Study in England. McNaughton, R., Lynn, E., Osborne, V., et al.[2018]

Citations

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Recombinant or Standard-Dose Influenza Vaccine in ... For the outcome of PCR-confirmed influenza among patients in the older age group, relative vaccine effectiveness was 14.4% (95% CI, −1.1 to 27.5) ...

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Safety, efficacy, and immunogenicity of Flublok in the ... The trial data demonstrate that the higher antigen content in Flublok results in improved immunogenicity. Data further suggest improved efficacy and a slightly ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S0264410X25006589

Recombinant quadrivalent influenza vaccine (RIV) induces ... RIV's enhanced performance was particularly evident in its response to influenza A components, with notably higher immunogenicity against both A ...

4. academic.oup.com academic.oup.com/ofid/article/11/10/ofae559/7775992

Relative Effectiveness and Immunogenicity of Quadrivalent ... Immunogenicity studies suggest that recombinant influenza vaccine (RIV) may provide better protection against influenza than standard-dose inactivated influenza ...

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Flublok® Influenza Vaccine | Sanofiflu - Sanofi campus IN A RANDOMIZED, CONTROLLED TRIAL VS FLUARIX: 30% RELATIVE REDUCTION IN PCR-CONFIRMED FLU IN ADULTS AGED 50+1,2. Study Design. Phase 3-4 randomized, controlled ...

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Package Insert - Flublok Clinical safety data for Flublok are presented from four clinical trials (Studies 1, 2, 3, and. 4). Data from a placebo-controlled trial in adults 18 through ...

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SAFETY DATA SHEET Flublok Influenza Vaccine. Toxicity to fish. No data available for mixture. Flublok Influenza Vaccine. Toxicity to daphnia and other aquatic invertebrates. No ...

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Influenza Vaccines Brochures and Resources | Sanofiflu This printable document contains the pivotal trial data, real-world evidence, and safety data for Flublok—including data from a real-world safety study in ...

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Flublok Labeling Updated With New Safety Data for ... The Food and Drug Administration (FDA) has approved updated labeling for Flublok (influenza vaccine) to include new safety data involving pregnant individuals.