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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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05077254
Recruitment Status : Not yet recruiting
First Posted : October 14, 2021
Last Update Posted : November 5, 2021
Sponsor:
Collaborator:
PPD
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.


Condition or disease Intervention/treatment Phase
Kidney Transplant Recipients Liver Transplant Recipients Biological: Pfizer-BioNTech COVID-19 Vaccine Booster Biological: Moderna COVID-19 Vaccine Booster 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 negative or indeterminate (<0.8 U/mL) anti-spike antibody (as measured by the Roche Elecsys® anti-SARS-CoV-2 S assay) after at least two mRNA COVID-19 vaccines.

Participants will be randomized to either:

  1. Receive an additional 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 an additional dose (booster) of mRNA-based COVID-19 vaccine.

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

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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:

  • An additional dose of COVID-19 vaccine only, or
  • Immunosuppression (IS) reduction plus an additional dose of 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
Estimated Study Start Date : November 2021
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Pfizer-BioNTech COVID-19 Vaccine Booster + SOC IS Regimen

Participants will receive an additional dose (1 dose) of the Pfizer-BioNTech COVID-19 vaccine 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 Booster
Administration: One dose administered intramuscularly.
Other Names:
  • Comirnaty®
  • mRNA COVID-19 vaccine
  • BNT162b2 mRNA COVID-19 vaccine
  • SARS-CoV-2 RNA vaccine

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 Booster+SOC IS Reduction

Participants will receive an additional dose (1 dose) of the Pfizer-BioNTech COVID-19 vaccine, 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 Booster
Administration: One dose administered intramuscularly.
Other Names:
  • Comirnaty®
  • mRNA COVID-19 vaccine
  • BNT162b2 mRNA COVID-19 vaccine
  • SARS-CoV-2 RNA vaccine

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 Booster + SOC IS Regimen

Participants will receive an additional dose (1 dose) of the Moderna COVID-19 Vaccine 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 Booster
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • Moderna COVID-19 vaccine
  • SARS-CoV-2 vaccine

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 Booster +SOC IS Reduction

Participants will receive an additional dose (1 dose) of the Moderna COVID-19 vaccine, 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 Booster
Administration: One dose administered intramuscularly.
Other Names:
  • mRNA COVID-19 vaccine
  • Moderna COVID-19 vaccine
  • SARS-CoV-2 vaccine

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




Primary Outcome Measures :
  1. Proportion of Participants Who Achieve an Antibody Response >50 U/mL [ Time Frame: Day 30 After Study Vaccination ]

    Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.

    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.



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. 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.

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 Francisco Health
San Francisco, California, United States, 94143
Contact: Dayana Shariff    415-476-4862    dayana.shariff@ucsf.edu   
Principal Investigator: Monica Fung, MD         
United States, Georgia
Emory Healthcare
Atlanta, Georgia, United States, 30322
Contact: Elizabeth Ferry    404-712-1816    Elizabeth.ferry@emoryhealthcare.org   
Principal Investigator: Stephanie M. Pouch, MD, MS         
United States, Illinois
University of Illinois Health
Chicago, Illinois, United States, 60612
Principal Investigator: Scott A. Borgetti, MD         
United States, Louisiana
Ochsner Health
New Orleans, Louisiana, United States, 70121
Principal Investigator: Jonathan M. Hand, MD         
United States, Maryland
Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit
Baltimore, Maryland, United States, 21287
Contact: Maggie Chahoud    860-810-6019    mchahou1@jhmi.edu   
Principal Investigator: William A. Werbel, MD         
United States, New York
Mt. Sinai Hospital
New York, New York, United States, 10029
Contact: Gina Carrara    212-659-8046    Gina.Carrara@mountsinai.org   
Principal Investigator: Rana M. Meenakshi, MD         
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
Principal Investigator: Cameron R. Wolfe, MD         
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
PPD
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
Additional Information:
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: November 5, 2021
Last Verified: November 2021
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