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COVID Protection After Transplant-Immunosuppression Reduction (CPAT-ISR)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05077254
Recruitment Status : Active, not recruiting
First Posted : October 14, 2021
Last Update Posted : March 29, 2024
Sponsor:
Collaborators:
PPD
Johns Hopkins University
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Study Description
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Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Kidney Transplant Recipients Liver Transplant Recipients Biological: Pfizer-BioNTech COVID-19 Vaccine 2023-2024 Biological: Moderna COVID-19 Vaccine 2023-2024 Drug: SOC IS Regimen Drug: SOC IS Reduction Phase 2

Detailed Description:

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 400 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized Study to Evaluate Antibody Response to an Additional Dose of SARS-CoV-2 Vaccination With and Without Immunosuppression Reduction in Kidney and Liver Transplant Recipients
Actual Study Start Date : December 6, 2021
Actual Primary Completion Date : February 28, 2024
Estimated Study Completion Date : March 4, 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: 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

 Biological: Pfizer-BioNTech COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • BNT162b2 mRNA COVID-19 vaccine
  • SARS-CoV-2 RNA vaccine
  • Comirnaty

Drug: SOC IS Regimen
Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.
Other Names:
  • Standard of Care transplant immunosuppression regimen
  • Immunosuppression (IS)
  • mycophenolate mofetil (MMF) or equivalent
  • tacrolimus
Experimental: 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

 Biological: Pfizer-BioNTech COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • BNT162b2 mRNA COVID-19 vaccine
  • SARS-CoV-2 RNA vaccine
  • Comirnaty

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.
Other Names:
  • Standard of Care (SOC) transplant immunosuppression regimen
  • Immunosuppression (IS) Reduction
  • mycophenolate mofetil (MMF) or equivalent
  • tacrolimus
Experimental: 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

 Biological: Moderna COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • Moderna COVID-19 vaccine
  • SARS-CoV-2 vaccine
  • Spikevax

Drug: SOC IS Regimen
Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.
Other Names:
  • Standard of Care transplant immunosuppression regimen
  • Immunosuppression (IS)
  • mycophenolate mofetil (MMF) or equivalent
  • tacrolimus
Experimental: 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

 Biological: Moderna COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • Moderna COVID-19 vaccine
  • SARS-CoV-2 vaccine
  • Spikevax

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.
Other Names:
  • Standard of Care (SOC) transplant immunosuppression regimen
  • Immunosuppression (IS) Reduction
  • mycophenolate mofetil (MMF) or equivalent
  • tacrolimus


Outcome Measures
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Primary Outcome Measures :
  1. The primary endpoint is the -fold increase in antibody titer (using the Roche Elecsys® anti-SARS-CoV-2 S assay) from before receiving the study dose of vaccine to 30 days after the study dose of vaccine. [ Time Frame: Day 30 After Study Vaccination ]
    Serum antibody titer will be measured using the Roche Elecsys®) severe acute respiratory syndrome coronavirus type 2 serological (anti-SARS-CoV-2) S assay.


Secondary Outcome Measures :
  1. Frequency of Solicited Local Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine [ Time Frame: Through Day 7 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  2. Frequency of Solicited Local Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine [ Time Frame: Through Day 7 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  3. Frequency of Solicited Systemic Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine [ Time Frame: Through Day 7 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  4. Frequency of Solicited Systemic Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine [ Time Frame: Through Day 7 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  5. Frequency of Any Serious Adverse Events (SAEs) [ Time Frame: Through Day 30 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  6. Frequency of Any Unsolicited Adverse Events (AEs) [ Time Frame: Through Day 30 Post Study Vaccination ]
    Safety measure. An AE associated with the receipt of the study's COVID-19 mRNA vaccine and/or study mandated procedures.

  7. Frequency of Any Serious Adverse Events (SAEs) [ Time Frame: Through Day 60 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  8. Frequency of Any Serious Adverse Events (SAEs) [ Time Frame: Through Day 365 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  9. Frequency of Any Unsolicited Adverse Events (AEs) [ Time Frame: Through Day 365 Post Study Vaccination ]
    Safety measure. An AE associated with the receipt of of the study's COVID-19 mRNA vaccine and/or study mandated procedures.

  10. Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection [ Time Frame: Through Day 60 Post Study Vaccination ]
    Safety measure post receipt of the study's COVID-19 mRNA vaccine.

  11. Proportion of Participants who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody [ Time Frame: Through Day 60 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  12. Proportion of Participants with Graft Loss [ Time Frame: Through Day 60 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  13. Occurrence of Death Among Participants [ Time Frame: Through Day 60 Post Study Vaccination ]
    Safety measure after receipt of the study's COVID-19 mRNA vaccine.

  14. Frequency of Positive SARS-CoV-2 Test Results Using Real-Time Polymerase Chain Reaction (RT-PCR) [ Time Frame: Baseline (Day 0, Prior to Study Vaccination), Month 1, 3, 6, 9 and 12 ]
    A nasal mid-turbinate swab for SARS-CoV-2 PCR testing will be collected prior to administration of the COVID-19, at specified timepoints after receipt of vaccination and, in any case of suspected COVID-19 infection.

  15. Occurrence of Symptomatic COVID-19 [ Time Frame: Through Day 365 Post Study Vaccination ]
    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.

  16. Occurrence of COVID-19 Requiring Hospitalization [ Time Frame: Through Day 365 Post Study Vaccination ]
    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.

  17. Change from Baseline in Anti-SARS-CoV-2 Antibody Levels at Day 30 [ Time Frame: Baseline (Day 0, Prior to Study Vaccination),Day 30 After Study Vaccination ]
    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.

  18. Change from Baseline in SARS-CoV-2 Antibody Levels [ Time Frame: From Baseline (Day 0, Prior to Study Vaccination) to Day 365 Post Study Vaccination ]
    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.

  19. Fold Increase in SARS-CoV-2 Antibody Levels: Limited to Participants With Detectable Antibody Levels at Baseline (Day 0) [ Time Frame: Baseline (Day 0, Prior to Receipt of COVID-19 Study Vaccination), Day 30 After Study Vaccination ]
    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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. 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.

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. 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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05077254


Locations
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United States, California
University of California, San Diego
San Diego, California, United States, 92093
University of California San Francisco Health
San Francisco, California, United States, 94143
United States, Georgia
Emory Healthcare
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Illinois Health
Chicago, Illinois, United States, 60612
Northwestern University
Evanston, Illinois, United States, 60208
United States, Iowa
University of Iowa Hospitals
Iowa City, Iowa, United States, 52242
United States, Louisiana
Ochsner Health
New Orleans, Louisiana, United States, 70121
United States, Maryland
Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit
Baltimore, Maryland, United States, 21287
United States, New York
NYU Langone Transplant Institute
New York, New York, United States, 10016
Mt. Sinai Hospital
New York, New York, United States, 10029
Weill Cornell Medicine
New York, New York, United States, 10065
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15260
United States, Texas
Houston Methodist
Houston, Texas, United States, 77030
United States, Wisconsin
University of Wisconsin-Madison
Madison, Wisconsin, United States, 53706
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
PPD
Johns Hopkins University
Investigators
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Study Chair: Dorry L. Segev, MD, PhD Transplant Surgery, Johns Hopkins University School of Medicine
Study Chair: Peter S. Heeger, MD Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai
Study Chair: Christian P. Larsen, MD, DPhil Emory Transplant Center, Emory University School of Medicine
More Information
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Publications:

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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT05077254    
Other Study ID Numbers: DAIT COVID19-TB-03
U01AI138897 ( U.S. NIH Grant/Contract )
NIAID CRMS ID#: 38892 ( Other Identifier: DAIT NIAID )
First Posted: October 14, 2021    Key Record Dates
Last Update Posted: March 29, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The plan is to share data upon completion of the study in: Immunology Database and Analysis Portal (ImmPort), a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts.
Time Frame: On average, within 24 months after database lock for the trial.
Access Criteria: Open access.
URL: https://www.immport.org/home

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
mRNA COVID-19 vaccines
SARS-CoV-2 antibody response
immunosuppression (IS)
coronavirus infectious disease 19
 COVID-19
severe acute respiratory syndrome coronavirus type 2
SARS-CoV-2 protection
Additional relevant MeSH terms:
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Mycophenolic Acid
Vaccines
Tacrolimus
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Calcineurin Inhibitors
Enzyme Inhibitors
 Molecular Mechanisms of Pharmacological Action
Antibiotics, Antineoplastic
Antineoplastic Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Anti-Infective Agents