COVID Protection After Transplant-Immunosuppression Reduction

NCT ID: NCT05077254

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

48 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-06

Study Completion Date

2025-02-21

Brief Summary

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This study will enroll individuals who have:

* Completed primary series of mRNA COVID-19 vaccine, and
* An antibody response ≤ 2500 U/mL 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.

Detailed Description

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This study is a randomized, open-label multi-site trial designed to induce an enhanced antibody response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) in kidney and liver transplant recipients who have ≤ 2500 U/mL anti-spike antibody (as measured by the Roche Elecsys® anti-SARS-CoV-2 S assay) after a completed primary series (3 doses) of mRNA COVID-19 vaccines.

Participants will be randomized to either:

1. Receive a study dose of mRNA based COVID-19 vaccine (booster) with no change in their immunosuppressive regimen, or
2. Undergo a temporary, prescribed reduction in their maintenance immunosuppression (IS) regimen and receive a study dose (booster) of mRNA based COVID-19 vaccine.

Protocol Version 8.0 will include a booster dose of either Pfizer-BioNTech COVID-19 Vaccine 2023-2024 or Moderna COVID-19 Vaccine 2023-2024, with or without IS reduction.

Duration of study participation for interested and eligible individuals: 13 months.

Conditions

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Kidney Transplant Recipients Liver Transplant Recipients

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants will be randomized to:

* A study dose of mRNA COVID-19 vaccine only, or
* Immunosuppression (IS) reduction plus a study dose of mRNA COVID-19 vaccine. IS reduction will be based on the participant's IS regimen upon study entry, in accordance with the study's protocol.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Regimen

Participants will receive a study dose (1 dose) of the Pfizer-BioNTech COVID-19 Vaccine 2023-2024 and will continue to take their standard of care transplant immunosuppressive medications without alterations in schedule and dosing.

SOC IS: Standard of Care transplant immunosuppression regimen

Group Type EXPERIMENTAL

Pfizer-BioNTech COVID-19 Vaccine 2023-2024

Intervention Type BIOLOGICAL

Administration: One dose administered intramuscularly.

SOC IS Regimen

Intervention Type DRUG

Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.

Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Reduction

Participants will receive an additional dose (1 dose) of the Pfizer-BioNTech COVID-19 Vaccine 2023-2024, with concurrent reduction of their standard of care transplant immunosuppression regimen (IS), per protocol.

SOC IS Reduction: Standard of Care transplant immunosuppression regimen reduction, per protocol

Group Type EXPERIMENTAL

Pfizer-BioNTech COVID-19 Vaccine 2023-2024

Intervention Type BIOLOGICAL

Administration: One dose administered intramuscularly.

SOC IS Reduction

Intervention Type DRUG

Participants will reduce their standard of care immunosuppression medications (IS) before and after the COVID-19 vaccine booster (1 dose), per protocol instruction.

Moderna COVID-19 Vaccine 2023-2024 + SOC IS Regimen

Participants will receive an additional dose (1 dose) of the Moderna COVID-19 Vaccine 2023-2024 and will continue to take their standard of care transplant immunosuppressive medications without alterations in schedule and dosing.

SOC IS: Standard of Care transplant immunosuppression regimen

Group Type EXPERIMENTAL

Moderna COVID-19 Vaccine 2023-2024

Intervention Type BIOLOGICAL

Administration: One dose administered intramuscularly.

SOC IS Regimen

Intervention Type DRUG

Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.

Moderna COVID-19 Vaccine 2023-2024 + SOC IS Reduction

Participants will receive a study dose (1 dose) of the Moderna COVID-19 Vaccine 2023-2024, with concurrent reduction of their standard of care transplant immunosuppression regimen (IS), per protocol.

SOC IS Reduction: Standard of Care transplant immunosuppression regimen reduction, per protocol

Group Type EXPERIMENTAL

Moderna COVID-19 Vaccine 2023-2024

Intervention Type BIOLOGICAL

Administration: One dose administered intramuscularly.

SOC IS Reduction

Intervention Type DRUG

Participants will reduce their standard of care immunosuppression medications (IS) before and after the COVID-19 vaccine booster (1 dose), per protocol instruction.

Interventions

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Pfizer-BioNTech COVID-19 Vaccine 2023-2024

Administration: One dose administered intramuscularly.

Intervention Type BIOLOGICAL

Moderna COVID-19 Vaccine 2023-2024

Administration: One dose administered intramuscularly.

Intervention Type BIOLOGICAL

SOC IS Regimen

Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.

Intervention Type DRUG

SOC IS Reduction

Participants will reduce their standard of care immunosuppression medications (IS) before and after the COVID-19 vaccine booster (1 dose), per protocol instruction.

Intervention Type DRUG

Other Intervention Names

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mRNA COVID-19 vaccine BNT162b2 mRNA COVID-19 vaccine SARS-CoV-2 RNA vaccine Comirnaty mRNA COVID-19 vaccine Moderna COVID-19 vaccine SARS-CoV-2 vaccine Spikevax Standard of Care transplant immunosuppression regimen Immunosuppression (IS) mycophenolate mofetil (MMF) or equivalent tacrolimus Standard of Care (SOC) transplant immunosuppression regimen Immunosuppression (IS) Reduction mycophenolate mofetil (MMF) or equivalent tacrolimus

Eligibility Criteria

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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. Individual ≥18 years of age.
3. Recipient of a kidney or liver transplant ≥12 months prior to enrollment, without allograft rejection in the 6 months preceding enrollment
4. Negative for anti-donor human leukocyte antigens (HLA) antibodies at screening (Central Lab Test Determination).
5. Currently taking one of the following tacrolimus-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
6. Received a minimum of 3 doses of either the Moderna coronavirus infectious disease 19 (COVID-19) vaccine or Pfizer-BioNTech COVID-19 vaccine
7. Participant must be ≥ 60 days after completion of primary vaccination or receipt of the most recent booster dose with any authorized or approved monovalent or bivalent COVID-19 vaccine at the time of study vaccine.
8. Serum antibody negative or low (titer ≤ 2500 U/mL) at ≥ 30 days from the last dose of mRNA COVID-19 vaccine and ≥ 30 days following receipt of a monoclonal antibody product or convalescent plasma for COVID-19, measured using the Roche Elecsys® anti-SARS-CoV-2 S assay.
9. Participant's transplant physician or midlevel practitioner who is clinically licensed to prescribe and manage immunosuppression must confirm the participant's eligibility based on medical history.

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. Prior receipt of the Moderna COVID-19 Vaccine 2023-2024 or Pfizer-BioNTech COVID-19 Vaccine 2023-2024.
6. Currently taking any systemic immunosuppressive agent, other than their prescribed transplant immunosuppression
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.

Exclusion Criteria

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

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PPD Development, LP

INDUSTRY

Sponsor Role collaborator

Johns Hopkins University

OTHER

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Dorry L. Segev, MD, PhD

Role: STUDY_CHAIR

Transplant Surgery, Johns Hopkins University School of Medicine

Peter S. Heeger, MD

Role: STUDY_CHAIR

Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai

Christian P. Larsen, MD, DPhil

Role: STUDY_CHAIR

Emory Transplant Center, Emory University School of Medicine

Locations

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University of California, San Diego

San Diego, California, United States

Site Status

University of California San Francisco Health

San Francisco, California, United States

Site Status

Emory Healthcare

Atlanta, Georgia, United States

Site Status

University of Illinois Health

Chicago, Illinois, United States

Site Status

Northwestern University

Evanston, Illinois, United States

Site Status

University of Iowa Hospitals

Iowa City, Iowa, United States

Site Status

Ochsner Health

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit

Baltimore, Maryland, United States

Site Status

NYU Langone Transplant Institute

New York, New York, United States

Site Status

Mt. Sinai Hospital

New York, New York, United States

Site Status

Weill Cornell Medicine

New York, New York, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status

Houston Methodist

Houston, Texas, United States

Site Status

University of Wisconsin-Madison

Madison, Wisconsin, United States

Site Status

Countries

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United States

References

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Werbel WA, Boyarsky BJ, Ou MT, Massie AB, Tobian AAR, Garonzik-Wang JM, Segev DL. Safety and Immunogenicity of a Third Dose of SARS-CoV-2 Vaccine in Solid Organ Transplant Recipients: A Case Series. Ann Intern Med. 2021 Sep;174(9):1330-1332. doi: 10.7326/L21-0282. Epub 2021 Jun 15. No abstract available.

Reference Type BACKGROUND
PMID: 34125572 (View on PubMed)

Related Links

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https://www.niaid.nih.gov/

National Institute of Allergy and Infectious Diseases

https://www.niaid.nih.gov/about/dait

Division of Allergy, Immunology, and Transplantation

Other Identifiers

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U01AI138897

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIAID CRMS ID#: 38892

Identifier Type: OTHER

Identifier Source: secondary_id

DAIT COVID19-TB-03

Identifier Type: -

Identifier Source: org_study_id

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