COVID-19 Protection After Transplant Pilot Study

Study Overview
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Brief Summary
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Antibodies are an important part of the body's defense against infection. Individuals who have no antibodies or very low antibody levels are considered less well protected from Coronavirus Disease 2019 (COVID-19) than those who have higher antibody levels. What level of antibodies is necessary for protection is currently unknown. Inadequate antibody response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccination has been described among kidney transplant recipients. The aim of this study is to elicit an antibody response to vaccination against SARS-CoV-2 in kidney transplant recipients who have failed to respond to two doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech Coronavirus Disease 2019 (COVID-19) vaccine.

Detailed Description
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This is an open label, non-randomized study in kidney transplant recipients who received two doses of either mRNA COVID-19 vaccine and have a negative (<0.8 U/mL) or low (titer <50 U/mL) SARS-CoV-2 antibody response using the Roche Elecsys® anti-RBD assay. Eligible participants will receive a third dose of the same mRNA vaccine as the prior two doses.

Official Title
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Immunogenicity of a Third Dose of Either the Moderna COVID-19 Vaccine or Pfizer-BioNTech COVID-19 Vaccine in Kidney Transplant Recipients Who Failed to Respond After Two Previous Doses

Conditions
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Kidney Transplant Recipients

Intervention / Treatment
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* Biological: mRNA-1273 vaccine (Pfizer/BioNTech)
* Biological: mRNA-1273 vaccine (Moderna)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals who meet all the following criteria are eligible for enrollment as study participants- Able to understand and provide informed consent; Recipient of kidney transplant ≥12 months prior to enrollment, without treated allograft rejection in the 6 months preceding enrollment; Received 2 doses of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine as specified in the respective Food and Drug Administration Emergency Use Authorization (FDA EUAs), >30 days and <8 months prior to enrollment ; and, Negative (antibody titer < 0.8U/mL) or low (antibodies detected at titer ≤ 50 U/mL) response to the vaccine at > 30 days from dose 2 of the Moderna COVID-19 vaccine or the Pfizer BioNTech vaccine, using the Roche Elecsys® anti-Receptor Binding Domain (RBD) assay. Exclusion Criteria: Individuals who meet any of these criteria are not eligible for enrollment as study participants- Recipient of any number of doses of any COVID vaccine product other than the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine; Known history of severe allergic reaction to any component of either the Moderna COVID-19 vaccine or Pfizer-BioNTech COVID-19 vaccine; Thrombotic events, myocarditis, or pericarditis temporally associated with prior dose of COVID-19 vaccine; Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months; Significant graft dysfunction; Receipt of any cellular depleting agent (e.g. ATG, Rituximab, Alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment; Receiving systemic immunomodulatory medication(s) for any condition other than transplant; Any untreated active infection, including BK viremia >10^4 copies; Infection with human immunodeficiency virus (HIV); Maintenance immunosuppressive regimen that includes belatacept or abatacept; Recent (within one year) or ongoing treatment for malignancy; or Any past or current medical problems, treatments, or findings which, in the opinion of the investigator, may pose additional risks from participation in the study, may interfere with the candidate's ability to comply with study requirements or may impact the quality or interpretation of the data obtained from the study.

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
Interventional Model Description: Open label, non-randomized.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: mRNA-1273 vaccine (Pfizer/BioNTech)<br>The mRNA-1273 vaccine was developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. Kidney transplant recipients who had a suboptimal antibody response to the standard two doses of vaccination with Pfizer/BioNTech will receive a third dose of the the same vaccine. Administration: One dose administered intramuscularly, upper arm. | Biological: mRNA-1273 vaccine (Pfizer/BioNTech)<br>* 30 microgram dose<br>* Other names: Pfizer-BioNTech COVID-19 vaccine;|
| Experimental: mRNA-1273 vaccine (Moderna)<br>The mRNA-1273 vaccine was developed to prevent COVID-19, the disease resulting from Severe Acute Respiratory Syndrome coronavirus (SARS-CoV-2) infection. Kidney transplant recipients who had a suboptimal antibody response to the standard two doses of vaccination with Moderna will receive a third dose of the same vaccine. Administration: One dose administered intramuscularly, upper arm. | Biological: mRNA-1273 vaccine (Moderna)<br>* 100 microgram dose<br>* Other names: Moderna COVID-19 vaccine;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Achieve an Antibody Response >50 U/mL | Efficacy measure status post third mRNA-1273 vaccination. | Day 30 Post-Vaccination (Dose 3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Solicited Local Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine | Safety measure status post third mRNA-1273 vaccination. | Through Day 7 Post-Vaccination (Dose 3) | 
| Frequency of Solicited Local Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine | Safety measure status post third mRNA-1273 vaccination. | Through Day 7 Post-Vaccination (Dose 3) | 
| Frequency of Solicited Systemic Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine | Safety measure status post third mRNA-1273 vaccination. | Through Day 7 Post-Vaccination (Dose 3) | 
| Frequency of Solicited Systemic Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine | Safety measure status post third mRNA-1273 vaccination. | Through Day 7 Post-Vaccination (Dose 3) | 
| Frequency of Any Serious Adverse Events (SAEs) | Safety measure status post third mRNA-1273 vaccination. | Through Day 30 Post-Vaccination (Dose 3) | 
| Frequency of Any Unsolicited Adverse Events (AEs) | Safety measure. An AE associated with the third dose of vaccine and/or study mandated procedures. | Through Day 30 Post-Vaccination (Dose 3) | 
| Frequency of Any Serious Adverse Events (SAEs) | Safety measure status post third mRNA-1273 vaccination. | Through Day 60 Post-Vaccination (Dose 3) | 
| Frequency of Any Serious Adverse Events (SAEs) | Safety measure status post third mRNA-1273 vaccination. | Through Day 365 Post-Vaccination (Dose 3) | 
| Frequency of Any Unsolicited Adverse Events (AEs) | Safety measure. An AE associated with the third dose of vaccine and/or study mandated procedures. | Through Day 365 Post-Vaccination (Dose 3) | 
| Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection | Safety measure status post third mRNA-1273 vaccination. | Through Day 60 Post-Vaccination (Dose 3) | 
| Proportion of Participants who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody | Safety measure status post third mRNA-1273 vaccination. | Through Day 60 Post-Vaccination (Dose 3) | 
| Proportion of Participants with Graft Loss | Safety measure status post third mRNA-1273 vaccination. | Through Day 60 Post-Vaccination (Dose 3) | 
| Occurrence of Death Among Participants | Safety measure status post third mRNA-1273 vaccination. | Through Day 60 Post-Vaccination (Dose 3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19 vaccine, SARS-CoV-2 antibody response