Impact of Immunosuppression Adjustment on COVID-19 Vaccination Response in Kidney Transplant Recipients

Study Overview
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Brief Summary
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Immunocompromised individuals, such as solid organ transplant (SOT) recipients are at high risk of COVID-19 associated complications and mortality. Retrospective studies so far have shown that a majority of SOT recipients did not develop appreciable anti-spike antibody response after a first, second, or even third dose of mRNA vaccine. Treatment with antimetabolites was associated with poor vaccine response. The goal of this study is 1) examine whether transient immunosuppression reduction improves the immune response to a third dose of SARS-CoV-2 mRNA vaccine in kidney transplant recipients and 2) to assess the safety of immunosuppression reduction before and after third dose SARS-CoV-2 mRNA vaccination.

Detailed Description
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This is a prospective, randomized open-labeled study of kidney transplant recipients who have previously received two doses of mRNA COVID-19 vaccine (either BNT162b2, Pfizer-BioNTech or mRNA-1273, Moderna) and who are eligible to receive a 3rd dose of mRNA vaccine.

Official Title
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Impact of Immunosuppression Adjustment on the Immune Response to SARS-CoV-2 mRNA Vaccination in Kidney Transplant Recipients (ADIVKT)

Conditions
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COVID-19, Immunosuppression, Vaccine Response Impaired

Intervention / Treatment
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* Drug: Reduction in antimetabolite immunosuppression


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is willing and able to give informed consent for participation in the study First or repeat kidney transplant recipient Negative or low positive antibody titer on SARS-CoV-2 antibody assay On a mycophenolate or azathioprine based immunosuppressive regimen > 6 months post-transplant Exclusion Criteria: Pregnancy Contraindication to SARS-CoV-2 vaccination (severe allergic reactions or anaphylaxis)

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
Interventional Model Description: Prospective randomized open-labeled
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunosuppression reduction<br>Reduction of immunosuppression before and after administration of a third dose of SARS-CoV-2 mRNA vaccine | Drug: Reduction in antimetabolite immunosuppression<br>* Reduction in dose in mycophenolate mofetil/mycophenolic acid (MMF) or azathioprine before and after receiving 3rd dose vaccination<br>|
| No Intervention: Standard of care<br>No change to immunosuppression before or after receipt of a third dose of SARS-Co-2 mRNA vaccine | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in anti-SARS-CoV-2 IgG titer to SARS-CoV-2 target proteins from baseline |  | 6 weeks after receipt of 3rd dose mRNA vaccine | 
| Percentage of participants who achieve high-positive antibody titer |  | 6 weeks after receipt of 3rd dose mRNA vaccine | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute rejection |  | 1 week to 16 weeks after intervention | 
| De Novo donor specific antibody (DSA) development |  | 4 week to 16 weeks after intervention | 
| Change in donor-derived cell free DNA from baseline |  | 1 week to 16 weeks after intervention | 
| Change in glomerular filtration rate (GFR) from baseline |  | 1 week to 16 weeks after intervention | 
| Change in proteinuria from baseline |  | 1 week to 16 weeks after intervention |