Seasonal Influenza Vaccine High Dose Boosting in Solid Organ Transplant Recipients

Study Overview
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Brief Summary
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In solid organ transplant (SOT) the receipt of influenza vaccine in an influenza season is associated with decreased disease severity as demonstrated by the presence of pneumonia and ICU admissions. Different strategies have been assessed to optimize vaccine efficacy and immunogenicity of the influenza vaccine in the solid organ transplant recipient (SOTR). The primary objective of the study is to evaluate the immunogenicity of 2 doses of the high dose influenza vaccine utilizing neutralizing antibody assays. A control group receiving 1 HD influenza vaccine will be included.

Official Title
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Seasonal Influenza Vaccine High Dose Boosting in Solid Organ Transplant Recipients

Conditions
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Solid Organ Transplant

Intervention / Treatment
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* Drug: Fluzone High-Dose Quadrivalent- 2 doses
* Drug: Fluzone High-Dose Quadrivalent- 1 dose of HD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: >=18 years old who underwent a solid organ transplant (Liver, lung, heart, kidney, pancreas) > 1 year prior to enrollment At least 1-year post-transplant Able and willing to provide informed consent Able and willing to undergo all study activities throughout the duration of the study Exclusion Criteria: Confirmed pregnancy Receipt of ATG or carfilzomib within the past 3 months Receipt of rituximab within the past 3 months Receipt of basiliximab within the past 3 months Prednisone dose >= 20 mg/day at the time of enrollment History of a severe allergy to influenza vaccine (i.e. Guillain Barre syndrome, anaphylaxis or angioedema)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: booster group<br>Participants who have undergone a solid organ transplant will receive two doses of an inactivated high dose influenza vaccine | Drug: Fluzone High-Dose Quadrivalent- 2 doses<br>* 2 doses of the High-Dose (HD) influenza vaccine separated by 4-6 weeks<br>|
| Active Comparator: Control group<br>Participants who have undergone a solid organ transplant will receive one dose of inactivated high dose influenza vaccine followed by a placebo injection | Drug: Fluzone High-Dose Quadrivalent- 1 dose of HD<br>* 1 dose of the High Dose (HD) influenza vaccine, followed by a placebo injection 4-6 weeks later<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutralizing antibody levels- Immunogenicity | Geometric mean titers and geometric mean fold rise from baseline of homologue neutralizing antibodies in reporter microneutralization will be measured and compared across groups. | Baseline | 
| Neutralizing antibody levels- Immunogenicity | Geometric mean titers and geometric mean fold rise from baseline of homologue neutralizing antibodies in reporter microneutralization will be measured and compared across groups. | 4-6 weeks after dose 1 | 
| Neutralizing antibody levels- Immunogenicity | Geometric mean titers and geometric mean fold rise from baseline of homologue neutralizing antibodies in reporter microneutralization will be measured and compared across groups. | 3 months after 2nd dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| clinical outcome- pneumonia | assess clinical outcome associated with an influenza infection such as pneumonia rates during the 2023-2024 and 2024-2025 influenza seasons. | 2 years | 
| clinical outcome- hospitalization rates | assess clinical outcome associated with an influenza infection such as hospitalization rates during the 2023-2024 and 2024-2025 influenza seasons. | 2 years | 
| clinical outcome- ICU admissions | assess clinical outcome associated with an influenza infection such as ICU admission rates during the 2023-2024 and 2024-2025 influenza seasons. | 2 years | 
| clinical - death rates | assess clinical outcome associated with an influenza infection such as death rates during the 2023-2024 and 2024-2025 influenza seasons. | 2 years |