COVID Protection After Transplant-Immunosuppression Reduction

• Status: Not yet recruiting
• Trial end date: 2023-03-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will enroll individuals who have:

• Completed, at a minimum, a full 2-dose course of either the Moderna messenger RNA (mRNA) based coronavirus infectious disease 19 (COVID-19) vaccine or the Pfizer-BioNTech mRNA based COVID-19 vaccine, and

• A negative or indeterminate (<0.8 U/mL) antibody response measured at least 30 days after the last dose of vaccine.

This group of patients is at high risk for severe COVID-19 disease due to pharmacologic immunosuppression and a high prevalence of non-transplant risk factors such as obesity and diabetes.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborator: PPD
• Treatments: Mycophenolic Acid; Tacrolimus; Vaccines

Criteria

Inclusion Criteria:

Individuals who meet all the following criteria are eligible for enrollment as study participants-

1. Able to understand and provide informed consent

2. Recipient of a kidney or liver transplant ≥12 months prior to enrollment, without allograft rejection in the 6 months preceding enrollment

3. Negative for anti-donor human leukocyte antigens (HLA) antibodies at screening (Central Lab Test Determination).

4. Currently taking one of the following calcineurin inhibitors (CNI)-based immunosuppressive regimens:

• Tacrolimus plus Mycophenolate Mofetil (MMF) or Mycophenolic Acid (MPA), with or without a corticosteroid

• Tacrolimus with trough ≥ 5ng/mL with or without ≤5 mg of prednisone or equivalent

5. Received a minimum of 2 doses of either the Moderna coronavirus infectious disease 19 (COVID-19) vaccine or Pfizer-BioNTech COVID-19 vaccine at least 30 days prior to study entry

6. Serum antibody negative or indeterminate (titer <0.8 U/mL) at ≥ 30 days from the last dose of mRNA COVID-19 vaccine, measured using the Roche Elecsys®) severe acute respiratory syndrome coronavirus type 2 serological (anti-SARS-CoV-2) S assay, and

7. Participant's transplant physician must confirm the participant's eligibility based on medical history and concur with the plan for immunosuppression modification.

Exclusion Criteria:

Individuals who meet any of these criteria are not eligible for enrollment as study participants-

1. Currently on an immunosuppressive regimen different from the three regimens described in the Inclusion Criteria, for example (but not limited to) those including sirolimus, everolimus, belatacept, or azathioprine

2. Recipient of any allograft other than a kidney or liver

3. Participant is pregnant

4. Any past history of Donor Specific Antibody (DSA) using local site standards

5. Currently taking any systemic immunosuppressive agent, other than their prescribed transplant immunosuppression

6. Recipients of any COVID-19 vaccine other than the Moderna COVID-19 vaccine or the Pfizer-BioNTech COVID-19 vaccine

7. Known history of severe allergic reaction to any component of an authorized or licensed COVID-19 vaccine

8. Thrombotic events, myocarditis, or pericarditis temporally associated with a prior dose of COVID-19 vaccine

9. History of heparin-induced thrombocytopenia

10. Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months

11. More than minimal graft dysfunction, in accordance with study definition

12. Receipt of any cellular depleting agent (e.g. antithymocyte globulins (ATG), rituximab, alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment

13. Concurrent autoimmune disease at risk for exacerbation with immunosuppression reduction

14. Any untreated active infection including BK viremia >10^4 copies

15. Infection with human immunodeficiency virus (HIV)

16. Recent (within one year) or ongoing treatment for malignancy with the exception of:

• Non- melanomatous skin cancer definitively treated by local therapy, and

• Definitively treated carcinoma-in-situ of the cervix (Stage 0 cervical cancer)

17. Treatment or prophylaxis of COVID-19 with a monoclonal antibody product or convalescent plasma within 6 months preceding enrollment, or

18. 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,

• interfere with the candidate's ability to comply with study requirements, or

• impact the quality or interpretation of the data obtained from the study.