High vs Standard Dose Flu Vaccine for Solid Organ Transplant Recipients

Overseen By Laura Stewart, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Disqualifiers: HIV, Pregnancy, Lung transplant, 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: 6-8 weeks

396 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have received CMVIG, IVIG, or SCIG in the 28 days before the first vaccination, or plan to receive them within 84-126 days after, you may not be eligible.

Is the high-dose flu vaccine safe for humans?

The high-dose flu vaccine, including Fluzone High-Dose, has been studied in various age groups and is generally safe. Most reported side effects are mild, like injection site reactions, fever, headache, and nausea, with serious events being rare. No new safety concerns have been identified in recent studies. ^{1 2 3 4 5}

How does the high-dose flu vaccine differ from the standard-dose for organ transplant patients?

The high-dose flu vaccine contains more antigens (substances that trigger an immune response) than the standard-dose, which may lead to better protection for solid organ transplant recipients who often have weaker immune responses. ^{1 4 6 7 8}

What is the purpose of this trial?

The influenza virus is a significant cause of morbidity in adult solid organ transplant (SOT) recipients. However, these individuals show a suboptimal response to vaccines including the standard-dose (SD) inactivated influenza vaccine (IIV). Recent studies have investigated two strategies to overcome poor immune responses in SOT recipients: (1) administration of high-dose (HD)-IIV compared to SD-IIV and (2) two doses of SD-IIV compared to one dose of SD-IIV in the same influenza season. The first study compared HD-IIV vs. SD-IIV in adult SOT and noted HD-IIV was safe and reported higher immunogenicity; however, the median post-transplant period was 38 months. In another phase II trial of adult SOT recipients, two doses of SD-IIV a month apart compared to one-dose SD-IIV revealed increased immunogenicity, with a median post-transplantation period of 18 months. Therefore, these studies lack evaluation in the early post-transplantation period in this vulnerable population when influenza disease is most severe. The administration of two-doses of HD-IIV in the same influenza season has also not been studied in SOT recipients. Moreover, the vast majority of SOT influenza vaccinations studies have not substantively evaluated prolonged immunogenicity. Thus, the optimal immunization strategy for SOT recipients less than 12 months post-transplant is poorly-defined. In addition, the immunologic predictors and correlates of influenza vaccine immunogenicity in SOT recipients have not been defined. The investigators hypothesize that adult solid organ transplant recipients that are 1-11 months out from transplant and are receiving high-dose inactivated influenza vaccine will have higher hemagglutination inhibition (HAI) geometric mean titers to influenza A antigens compared to adult SOT recipients receiving standard-dose inactivated influenza vaccine. To test this hypothesis and address the above critical knowledge gaps, The investigators propose to conduct a phase II multicenter randomized controlled trial comparing either two doses HD-IIV, two doses of SD-IIV, or one-dose of HD-IIV in adult kidney, heart, and liver SOT recipients 1-11 months post-transplantation. The results of this study will address significant gaps in knowledge regarding influenza vaccine strategies and immune responses in adult SOT recipients and will guide vaccine recommendations in this vulnerable population.

Eligibility Criteria

Adults aged 18+ who are 1-11 months post solid organ transplant (kidney, heart, liver) can join this trial. They must be reachable for follow-ups and not pregnant or have had lung/intestine transplants, severe vaccine allergies, low platelets, Guillain-Barre syndrome, HIV, or recent immunoglobulin therapy.

Inclusion Criteria

I have received a solid organ transplant, such as a kidney, heart, or liver.

I can be contacted by phone, email, or text.

I had an organ transplant between 1 and 12 months ago.

Exclusion Criteria

History of known severe latex hypersensitivity

You had a bad reaction to a flu shot in the past or have a severe allergy to eggs or egg products.

I have an active HIV infection.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either two doses of HD-IIV, two doses of SD-IIV, or one dose of HD-IIV followed by placebo

6-8 weeks

3 visits (in-person)

Follow-up

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

6 months

2 visits (in-person), weekly electronic/telephone communication

Treatment Details

Interventions

• High Dose Quadrivalent Inactivated Influenza Vaccine
• Standard Dose Quadrivalent Inactivated Influenza Vaccine

Trial Overview The study is testing if a high-dose flu vaccine gives better immunity than the standard dose in new organ transplant recipients. Participants will get either two high doses, two standard doses or one high dose of the flu shot to see which works best.

Participant Groups

Group I: Two Doses Standard Dose Quadrivalent Inactivated Influenza Vaccine Experimental Treatment 1 Intervention

two doses of 0.5 mL SD-IIV (15µg of each influenza antigen) 28-42 days apart

Group II: Two Doses High Dose Quadrivalent Inactivated Influenza Vaccine Experimental Treatment 1 Intervention

two doses of 0.7 mL HD-IIV (60µg of each influenza antigen) 28-42 days apart

Group III: One Dose High Dose Quadrivalent Inactivated Influenza Vaccine Experimental Treatment 1 Intervention

one dose of 0.7 mL HD-IIV (60µg of each influenza antigen) followed by placebo 28-42 days later

High Dose Quadrivalent Inactivated Influenza Vaccine is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Approved in Canada as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Approved in European Union as Fluzone High-Dose for:

• Influenza prevention in individuals 65 years and older

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Feinberg School of Medicine, Northwestern University

Collaborator

Trials

34

Recruited

12,300+

Northwestern University Feinberg School of Medicine

Collaborator

Trials

42

Recruited

15,500+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

University of Washington

Collaborator

Trials

1,858

Recruited

2,023,000+

Findings from Research

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]

The high-dose quadrivalent influenza vaccine (QIV-HD) was approved for individuals 65 years and older, and a review of 2,122 adverse event reports showed that 95.1% were non-serious, aligning with findings from prelicensure trials.

No new safety concerns were identified, with the most common serious events being Guillain-Barré syndrome and local reactions, suggesting that QIV-HD is a safe option for preventing influenza in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Woo, EJ., Moro, PL.[2022]

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 high-dose quadrivalent inactivated influenza vaccine (HD-QIV) demonstrated excellent immunogenicity in healthy adults aged 19-64, achieving 100% seroprotection for A/H1N1 and high seroconversion rates for other strains, indicating strong immune response.

The HD-QIV was found to be safe and well-tolerated, with no serious adverse events reported, making it a promising option for enhancing influenza protection in the adult population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults. Noh, JY., Jang, YS., Lee, SN., et al.[2020]

In a study involving 2100 adults aged 60 and older, the high-dose quadrivalent influenza vaccine (IIV4-HD) administered intramuscularly showed superior immune responses compared to the standard-dose vaccine (IIV4-SD) given subcutaneously, indicating better protection against influenza.

Both vaccines had similar safety profiles, with IIV4-HD being well tolerated and no significant safety concerns identified, suggesting it is a safe option for older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults ≥ 60 years of age: Results from a phase III, randomized clinical trial. Sanchez, L., Nakama, T., Nagai, H., et al.[2023]

The high-dose influenza vaccine (QIV-HD) demonstrated significantly higher immune responses compared to the standard-dose vaccine (QIV-SD) in older adults, with greater geometric mean titers for all four influenza strains tested.

Both QIV-HD and QIV-SD had similar safety profiles, indicating that the high-dose vaccine is not only more effective but also safe for use in individuals aged 65 and older.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study. Chen, JY., Hsieh, SM., Hwang, SJ., et al.[2023]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of high doses of quadrivalent influenza vaccine in children 6 months through [2021]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Postmarketing safety surveillance of high-dose quadrivalent influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

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

4. Netherlands 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. [2020]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Randomized, single-blind, active-controlled phase I clinical trial to evaluate the immunogenicity and safety of GC3114 (high-dose, quadrivalent influenza vaccine) in healthy adults. [2020]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Superior immunogenicity of high-dose quadrivalent inactivated influenza vaccine versus Standard-Dose vaccine in Japanese Adults ≥ 60 years of age: Results from a phase III, randomized clinical trial. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients. [2022]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Immunogenicity and safety of high-dose quadrivalent influenza vaccine in older adults in Taiwan: A phase III, randomized, multi-center study. [2023]