COVID Protection After Transplant-Immunosuppression Reduction

Phase 2

Active, not recruiting

• Conditions: Kidney Transplant Recipients; Liver Transplant Recipients
• Interventions: Biological: Pfizer-BioNTech COVID-19 Vaccine 2023-2024; Biological: Moderna COVID-19 Vaccine 2023-2024; Drug: SOC IS Regimen; Drug: SOC IS Reduction

• Registration Number: NCT05077254
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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.

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 Timeline

• Study First Submitted: 2021-10-12
• Study First Submitted QC: 2021-10-12
• Study First Posted: 2021-10-14
• Study Start: 2021-12-06
• Primary Completion: 2024-02-28
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-27
• Last Update Posted: 2024-03-29
• Study Completion: 2025-03-04

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 400

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Regimen	Pfizer-BioNTech COVID-19 Vaccine 2023-2024	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
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Regimen	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
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Reduction	Pfizer-BioNTech COVID-19 Vaccine 2023-2024	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
Pfizer-BioNTech COVID-19 Vaccine 2023-2024 + SOC IS Reduction	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
Moderna COVID-19 Vaccine 2023-2024 + SOC IS Regimen	Moderna COVID-19 Vaccine 2023-2024	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
Moderna COVID-19 Vaccine 2023-2024 + SOC IS Regimen	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
Moderna COVID-19 Vaccine 2023-2024 + SOC IS Reduction	Moderna COVID-19 Vaccine 2023-2024	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
Moderna COVID-19 Vaccine 2023-2024 + SOC IS Reduction	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

Primary Outcome Measures

Name	Time	Method
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.	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

Name	Time	Method
Frequency of Positive SARS-CoV-2 Test Results Using Real-Time Polymerase Chain Reaction (RT-PCR)	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.
Occurrence of Symptomatic COVID-19	Through Day 365 Post Study Vaccination	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.
Occurrence of COVID-19 Requiring Hospitalization	Through Day 365 Post Study Vaccination	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.
Change from Baseline in Anti-SARS-CoV-2 Antibody Levels at Day 30	Baseline (Day 0, Prior to Study Vaccination),Day 30 After Study Vaccination	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.
Frequency of Any Serious Adverse Events (SAEs)	Through Day 365 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Frequency of Any Unsolicited Adverse Events (AEs)	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.
Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection	Through Day 60 Post Study Vaccination	Safety measure post receipt of the study's COVID-19 mRNA vaccine.
Proportion of Participants who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody	Through Day 60 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Proportion of Participants with Graft Loss	Through Day 60 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Change from Baseline in SARS-CoV-2 Antibody Levels	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.
Fold Increase in SARS-CoV-2 Antibody Levels: Limited to Participants With Detectable Antibody Levels at Baseline (Day 0)	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.
Frequency of Solicited Local Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Through Day 7 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Frequency of Solicited Systemic Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Through Day 7 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Frequency of Solicited Local Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Through Day 7 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Frequency of Solicited Systemic Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Through Day 7 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.
Occurrence of Death Among Participants	Through Day 60 Post Study Vaccination	Safety measure after receipt of the study's COVID-19 mRNA vaccine.

Trial Locations

Locations (15)

University of Illinois Health; 🇺🇸 Chicago, Illinois, United States

Emory Healthcare; 🇺🇸 Atlanta, Georgia, United States

University of California, San Diego; 🇺🇸 San Diego, California, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

Houston Methodist; 🇺🇸 Houston, Texas, United States

Northwestern University; 🇺🇸 Evanston, Illinois, United States

University of Iowa Hospitals; 🇺🇸 Iowa City, Iowa, United States

Weill Cornell Medicine; 🇺🇸 New York, New York, United States

Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit; 🇺🇸 Baltimore, Maryland, United States

Ochsner Health; 🇺🇸 New Orleans, Louisiana, United States

NYU Langone Transplant Institute; 🇺🇸 New York, New York, United States

Mt. Sinai Hospital; 🇺🇸 New York, New York, United States

University of Wisconsin-Madison; 🇺🇸 Madison, Wisconsin, United States

University of California San Francisco Health; 🇺🇸 San Francisco, California, United States