Seasonal Influenza Vaccines for Flu

Overseen By James J Kobie, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Disqualifiers: Guillain-Barre, Egg allergy, Malignancy, 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: 6

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to study how different approved flu vaccines affect the immune response, focusing on how antibodies respond to the vaccines. It involves several vaccines, such as Fluzone (Influenza Virus Vaccine) and Fluad (Adjuvanted Quadrivalent Inactivated Influenza Vaccine), with participants grouped by age and vaccine type. Healthy adults who haven't had respiratory infections in the past month and have no known allergy to flu vaccines make good candidates. As a Phase 4 trial, the treatment is already FDA-approved and proven effective, allowing researchers to understand how it benefits more patients.

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

The trial protocol does not specify whether you need to stop taking your current medications. However, it does exclude participants with certain medical conditions and recent vaccinations, so it's best to discuss your specific situation with the trial team.

What is the safety track record for these treatments?

Research has shown that all the flu vaccines in this study—Fluzone, Fluzone High-Dose, Flucelvax, and Fluad—are safe, as they have already received FDA approval.

Fluzone and Fluzone High-Dose do not contain any live flu virus, so they cannot cause the flu. Some individuals might experience mild soreness or swelling at the injection site, but serious side effects are rare.

Flucelvax is also safe. In past studies, fewer than 1% of participants experienced serious side effects within a month of vaccination. Most people have only mild reactions, if any.

Fluad has been tested in over 10,000 adults aged 65 and older, demonstrating its safety and tolerability. Most side effects are mild and temporary, such as soreness at the injection site.

Overall, these vaccines have good safety records, indicating they are generally safe for most people. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these influenza vaccines because each offers unique benefits for different age groups. Flucelvax stands out as it is produced using cell culture technology instead of the traditional egg-based methods, which may result in a more effective vaccine for those 18–50 years old. Fluzone High-Dose and Fluad are designed specifically for older adults (65–80 years old), providing a higher dose or an adjuvanted formulation, respectively, to boost immune response in this age group. Each of these vaccines targets the flu virus differently, helping to enhance protection and effectiveness across varying populations.

What is the effectiveness track record for these seasonal influenza vaccines?

This trial will compare different influenza vaccines. Studies have shown that Fluzone High-Dose, one of the vaccines in this trial, is 24% more effective than regular flu shots at preventing the flu in adults aged 65 and older. Another vaccine in this trial, Flucelvax, a cell-based vaccine, significantly reduces doctor visits due to the flu compared to traditional egg-based vaccines. Research on Fluad, also part of this trial, includes an ingredient to boost the immune response and indicates it provides strong protection and lowers the risk of hospitalization in older adults. These vaccines are all FDA-approved and have proven effective in preventing the flu and related complications. ^{6 7 8 9 10}

Who Is on the Research Team?

James J Kobie, PhD

Principal Investigator

University of Alabama at Birmingham

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 18-50 and 65-80 who can consent to participate. They must weigh at least 110 lbs and not have a history of severe illnesses, recent heart attacks, strokes, or certain chronic diseases like dementia or lupus. Pregnant women, those with egg allergies, bleeding disorders, drug abuse issues (excluding marijuana), or immunodeficiencies are excluded.

Inclusion Criteria

I am between 65 and 80 years old.

I weigh at least 110 lbs.

Able to give informed consent

Exclusion Criteria

I had a moderate to severe illness after getting the flu shot within the last 6 weeks.

Refusal or inability to have blood drawn or participate in study procedures

I have a disorder where my lymphocytes are increasing abnormally.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive a single dose of the assigned influenza vaccine

1 day

1 visit (in-person)

Follow-up

Participants are monitored for antibody and B cell responses after vaccination

3 months

2 visits (in-person)

Second Year Vaccination

Participants receive a second dose of the influenza vaccine in the following year

1 day

1 visit (in-person)

Second Year Follow-up

Participants are monitored for antibody and B cell responses after the second year vaccination

3 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Fluad
• Flucelvax
• Fluzone
• Fluzone High-Dose

Trial Overview The study tests how different FDA-approved flu vaccines—Flucelvax, Fluzone High-Dose, Fluzone, Fluad—affect antibody responses in younger and older adults. It also looks at the impact of past vaccinations on these responses.

How Is the Trial Designed?

Group I: Fluzone Younger Active Control 1 Intervention

10 adults 18-50 years old, will receive a single dose of the Fluzone influenza vaccine each year for two sequential years

Group II: Flucelvax Active Control 1 Intervention

10 adults 18-50 years old, will receive a single dose of the Flucelvax influenza vaccine each year for two sequential years

Group III: Fluzone Older Active Control 1 Intervention

10 adults 65-80 years old, will receive a single dose of the Fluzone influenza vaccine

Group IV: Fluzone High Dose Active Control 1 Intervention

10 adults 65-80 years old, will receive a single dose of the Fluzone High-Dose influenza vaccine

Group V: Fluad Active Control 1 Intervention

10 adults 65-80 years old, will receive a single dose of the Fluad influenza vaccine

Fluad is already approved in United States, European Union for the following indications:

Approved in United States as FLUAD QUADRIVALENT for:

• Active immunization of persons 65 years of age and older against influenza disease caused by influenza virus subtypes A and types B contained in the vaccine

Approved in European Union as FLUAD for:

• Active immunization of persons 65 years of age and older against influenza disease caused by influenza virus subtypes A and types B contained in the vaccine

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Published Research Related to This Trial

The study successfully developed a Flurbiprofen sodium ocusert that enhances local drug delivery, potentially improving patient compliance with eye treatments.

The optimized ocuserts demonstrated stability at room temperature and showed a strong correlation between in vitro and in vivo drug release, indicating effective drug delivery mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design and evaluation of ocusert for controlled delivery of flurbiprofen sodium. Kulhari, H., Pooja, D., Narayan, H., et al.[2016]

The inactivated quadrivalent influenza vaccine (IIV4) was found to be safe and well-tolerated in a phase III trial involving 1,648 adults and 329 children/adolescents, with no serious adverse events reported.

IIV4 induced strong antibody responses to all four influenza strains it targets, meeting all immunogenicity criteria set by the European Medicines Agency, and showed comparable efficacy to the trivalent vaccine (IIV3) in both age groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity, and lot-to-lot consistency of a quadrivalent inactivated influenza vaccine in children, adolescents, and adults: A randomized, controlled, phase III trial. Cadorna-Carlos, JB., Nolan, T., Borja-Tabora, CF., et al.[2015]

The study successfully developed a long orodispersible film (ODF) containing warfarin sodium, which allows for safe and flexible dosing, making it easier for patients to manage their medication.

Using a continuous manufacturing process, the long ODF can be dispensed like tape, enabling individualized therapy for patients of all ages, enhancing the convenience and adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Formulation development of a continuously manufactured orodispersible film containing warfarin sodium for individualized dosing. Niese, S., Quodbach, J.[2019]

The fixed-dose combination (FDC) capsule of candesartan cilexetil, hydrochlorothiazide, and rosuvastatin (CC/HCTZ/RSV) demonstrated bioequivalence to the separate tablet formulations in a study involving 24 healthy subjects, indicating similar pharmacokinetics and effectiveness for cardiovascular disease prevention.

All adverse events reported during the study were mild, suggesting that the new FDC capsule formulation is safe and well-tolerated for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics of a new fixed-dose combination of candesartan cilexetil, hydrochlorothiazide, and rosuvastatin in healthy adult subjects. Yerino, GA., Feleder, EC., Halabe, EK., et al.[2022]

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 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]

The study successfully developed a nanoparticulate, instant orodispersible film (iODF) powder that allows for individualized dosing of active pharmaceutical ingredients (APIs), achieving high drug loads of 11.8 mg/cm² in the final films.

The iODF powders maintain their advantageous properties, including particle size and dissolution profiles, even after being stored for three months at various temperatures, ensuring stability and effectiveness of the medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Instant ODFs - Development of an intermediate, nanoparticle-based product platform for individualized medication. Steiner, D., Finke, JH., Kwade, A.[2018]

The quadrivalent influenza vaccine AdimFlu-S showed strong immunogenicity in a study of 174 healthy children aged 3 to 17, achieving high seroprotection rates above 96.4% for all vaccine strains.

The vaccine was well tolerated with no serious adverse events reported over a 6-month follow-up period, indicating it is a safe option for improving protection against different influenza B lineages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of a quadrivalent inactivated influenza vaccine in healthy subjects aged 3 to 17 years old: A phase III, open label, single-arm study. Chang, CY., Cho, CY., Lai, CC., et al.[2021]

Dexamethasone and fludrocortisone acetate are resistant to ionizing radiation at doses of 25-50 kGy, making them suitable for sterilization by radiation, while fluconazole is too sensitive and requires alternative sterilization methods.

Irradiation of these compounds resulted in a decrease in active substance content and the formation of radiolysis products, indicating that while some steroid derivatives can withstand radiation, fluconazole's stability is compromised, highlighting the need for careful selection of sterilization methods based on the compound's properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The effect of fluorine substituent on radiochemical stability of some steroid and azole derivatives]. Marciniec, B., Dettlaff, K., Bafeltowska, J.[2016]

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]

Citations

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Interim Estimates of 2024–2025 Seasonal Influenza ... Effectiveness against influenza A(H3N2) was 51% (IVY) against influenza-associated hospitalization but was not statistically significant in the ...

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

Comparable effectiveness of MF59®-adjuvanted and high- ... The CDC reported an overall vaccine effectiveness (VE) of 46%. In adults aged ≥65 years, absolute vaccine effectiveness was 41% (95% CI, 36-46%) in outpatient ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06029933

NCT06029933 | Fluad vs. Fluzone High-Dose Vaccine ... This study will evaluate the relative vaccine effectiveness of quadrivalent adjuvanted inactivated influenza vaccine (aIIV4) versus quadrivalent high-dose ...

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

New Data Supports the Effectiveness of Adjuvanted ... In this study, findings demonstrated that aTIV was associated with 12% lower risk of hospitalization and a 37% lower risk of respiratory-related ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11951413/

Enhanced influenza vaccines impact effectiveness in ... The introduction of adjuvanted QIV significantly improved influenza protection in individuals aged 65 and older in Denmark compared with standard-dose QIV. High ...

6. fda.gov fda.gov/files/vaccines,%20blood%20&%20biologics/published/Package-Insert-FLUAD-QUADRIVALENT_0.pdf

Package Insert - FLUAD QUADRIVALENT Study 1 (NCT02587221) was a multi-center, randomized, observer-blind, non- influenza comparator-controlled efficacy and safety study conducted in 12 countries ...

7. fda.gov fda.gov/media/179766/download

Package Insert - FLUAD The safety of FLUAD and FLUAD QUADRIVALENT was evaluated in 17 clinical studies in. 10,911 adults 65 years of age and older. Data for FLUAD QUADRIVALENT are ...

8. cdc.gov cdc.gov/vaccine-safety/vaccines/flu.html

Influenza (Flu) Vaccine Safety Findings from vaccine safety monitoring systems and scientific studies have shown that flu vaccines have an excellent safety profile. Hundreds ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10611124/

Immunogenicity and Safety of MF59-Adjuvanted ... The study showed the adjuvanted vaccine is safe and well tolerated and able to produce a strong immune response. Functional antibody responses ...

10. cslseqirus.us cslseqirus.us/news/seqirus-receives-fda-approval-for-fluad-quadrivalent-for-adults-65-years-and-older

Seqirus Receives FDA Approval for FLUAD® Quadrivalent ... FLUAD and FLUAD QUADRIVALENT are inactivated influenza vaccines indicated for active immunization against influenza disease caused by influenza virus subtypes A ...