Pilot Trial on Immunosuppression Modulation to Increase SARS-CoV-2 Vaccine Response in Kidney Transplant Recipients

Study Overview
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Brief Summary
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Mycophenolate has been identified as risk factor for non-response to SARS-CoV-2 vaccination in kidney transplant recipients. Safety and efficacy of temporarily stopping of mycophenolate (or azathioprine) to increase vaccine response has not been established. This is a non-randomized, controlled pilot study including up to 40 kidney transplant recipients not responding to at least three previous SARS-CoV-2 vaccine doses. Mycophenolate or azathioprine will be stopped for two weeks peri-vaccination starting one week before vaccination until one week after vaccination. Allocation to mycophenoalte or azathioprine discontinuation arm will be based on an overall risk assessment by the transplant physician and patient preference. Patients not stopping mycophenolate or azathioprine will serve as control group.

Official Title
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Pilot Trial on Immunosuppression Modulation in Kidney Transplant Recipients Without SARS-CoV-2 Spike Protein Antibodies Following Full Vaccination

Conditions
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COVID-19

Intervention / Treatment
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* Other: Immunosuppression reduction
* Other: No immunosuppression reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient has received a kidney transplantation > 18 years of age No SARS-CoV-2 spike protein antibodies four weeks after at least three previous vaccine doses Maintenance immunosuppression with mycophenolate or azathioprine Exclusion Criteria: acute illness with fever Prior documented infection with SARS-CoV-2 triple anticoagulation therapy Subject is currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug trial(s), or subject is receiving other investigational agent(s) Subject has known sensitivity or intolerance to any of the products to be administered for the purpose of this study Subject has any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with the study procedures Subject is pregnant or breast feeding SARS-CoV-2 spike protein antibodies four weeks after the 3rd last vaccination > 0.8 BAU/mL

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Immunosuppression reduction<br>Participants stop mycophenolate or azathioprine for two weeks peri-vaccination. Treatment is stopped on week before vaccination and only restarted one week after vaccination | Other: Immunosuppression reduction<br>* participants stop mycophenolate or azathioprine one week before additional vaccine dose. Overall medication is stopped for two weeks.<br>|
| Active Comparator: No immunosuppression reduction<br>no alterations to immunosuppression | Other: No immunosuppression reduction<br>* participants do not alter immunosuppresion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion at 4 weeks | Number of patients developing SARS-CoV-2 antibodies at 4 weeks after vaccination | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion at 7 days | Number of patients developing SARS-CoV-2 antibodies at 7 days after vaccination | 7 days | 
| Antibody levels at 4 weeks | SARS-CoV-2 antibody levels at 4 weeks after vaccination | 4 weeks | 
| Donor specific antibodies | Donor specific antibodies at 4 weeks after mycophenolate / azathioprine pausing | 4 weeks | 
| Donor-derived cell free DNA | Donor-derived at 4 weeks after mycophenolate / azathioprine pausing | 4 weeks | 
| Creatinine levels | Creatinine levels at 4 weeks after mycophenolate / azathioprine pausing | 4 weeks |