COVID-19 Protection After Transplant Pilot Study

Phase 2

Completed

Interventions: Biological: mRNA-1273 vaccine (Moderna)
Biological: BNT162b2 vaccine (Pfizer/BioNTech)

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
mRNA-1273 vaccine (Moderna)	mRNA-1273 vaccine (Moderna)	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.
BNT162b2 mRNA-based vaccine (Pfizer/BioNTech)	BNT162b2 vaccine (Pfizer/BioNTech)	The BNT162b2 mRNA-based 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.

Primary Outcome Measures

Name	Time	Method
Proportion of Recipients Who Achieve an Antibody Response >50 U/mL After the Third Dose of mRNA COVID-19 Vaccine	Outcome was measured at 30 days after study intervention (dose 3 vaccination)	The proportion of participants who achieve an antibody response \>50 U/mL after the third dose of vaccine using the Roche Elecsys® anti-RBD assay is considered to show positive response to the intervention, negative response otherwise.

Secondary Outcome Measures

Name	Time	Method
Frequency of/Proportion of Participants With Vaccine Reactogenicity (Local or Systemic) and/or Allergy to the mRNA-Based COVID-19 Vaccine	Through Day 7 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine
Frequency of/Proportion of Participants With Any Serious Adverse Events (SAEs) Following the Third Dose of an mRNA Vaccine	Through Day 30 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine
Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection (Clinical or Biopsy Proven)	Through Day 60 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine
Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody	Through Day 90 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine
Proportion of Participants With Graft Loss	Through Day 60 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine.
Occurrence of Death Among Participants	Through Day 60 Post-Vaccination (Dose 3)	Safety measure status post third dose of mRNA vaccine.