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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the best method for administering flu vaccines to individuals who have recently undergone a kidney, heart, or liver transplant. It compares three approaches: two high-dose shots, two standard-dose shots, or one high-dose shot. The goal is to determine if a high-dose vaccine (High Dose Quadrivalent Inactivated Influenza Vaccine) provides better flu protection for these individuals. Suitable candidates are those who have received a transplant within the last year and have not yet received this season’s flu shot. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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

Research has shown that the high-dose flu shot (HD-IIV) is generally safe and well-tolerated for organ transplant recipients. Studies have found that the high-dose shot enhances the immune response more effectively than the regular-dose (SD) vaccine. Side effects are similar to those of the regular-dose vaccine, such as mild soreness at the injection site.

For the regular-dose vaccine, research also indicates it is safe and generally well-tolerated in transplant patients. Although the immune response may not be as robust as with the high-dose vaccine, it remains an effective option with few side effects.

Both vaccines have been tested in transplant patients and are considered safe, with only mild side effects reported. This trial aims to determine which dose works best for individuals who have recently undergone a transplant. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for solid organ transplant recipients because they explore using high doses of the flu vaccine, which could offer stronger protection for this vulnerable group. Typically, flu vaccines for transplant patients are given in standard doses, but the high-dose option delivers four times the amount of each influenza antigen. This increased dosage may boost the immune response, providing better defense against the flu. By comparing both high and standard doses, researchers hope to determine the most effective approach to safeguarding transplant recipients from influenza.

What evidence suggests that this trial's treatments could be effective for solid organ transplant recipients?

This trial will compare the effectiveness of high-dose and standard-dose flu vaccines for solid organ transplant recipients. Research has shown that a high-dose flu vaccine might offer better protection for people with organ transplants. One study found that high-dose vaccines helped the body recognize and combat the flu virus more effectively. Another study showed that adult transplant recipients who received the high-dose vaccine were better protected than those who received the standard dose. In this trial, some participants will receive two doses of the high-dose vaccine, while others will receive two doses of the standard-dose vaccine. Additionally, one group will receive one dose of the high-dose vaccine followed by a placebo. For standard-dose vaccines, receiving two doses in one flu season improved the immune response compared to just one dose. This suggests that both higher doses and more frequent doses could be important in helping organ transplant recipients fight the flu. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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 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]

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]

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]

Citations

1. cdc.gov cdc.gov/acip/grade/influenza-solid-organ-transplant.html

Higher-Dose and Adjuvanted Influenza Vaccines for Solid ... A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients. Clin Infect Dis ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10724468/

Comparison of Two High-Dose Versus Two Standard- ... This study found that a 2-dose regimen of HD-TIV was associated with greater immunogenicity as compared to SD-QIV in adult HCT recipients and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04613206

High vs. Standard Dose Influenza Vaccine in Adult SOT ... The investigators hypothesize that adult solid organ transplant recipients that are 1-11 months out from transplant and are receiving high-dose inactivated ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1600613522281052

Influenza Vaccination in the Organ Transplant Recipient Vaccine has been shown to be safe and generally well tolerated in both adult and pediatric transplant recipients. However, responses to vaccine are variable and ...

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

Fluzone High-Dose Seasonal Influenza Vaccine The higher dose of antigen in the vaccine is intended to give people 65 years and older a better immune response to vaccination, and therefore, ...

6. academic.oup.com academic.oup.com/cid/article/66/11/1698/4743251

A Double-Blind, Randomized Trial of High-Dose vs Standard ... HD vaccine demonstrated significantly better immunogenicity than SD vaccine in adult transplant recipients and may be the preferred influenza vaccine for this ...