COVID Protection After Transplant-Immunosuppression Reduction

Kidney Transplant Recipients Clinical Trial

— CPAT-ISR  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05077254
• Other study ID #: DAIT COVID19-TB-03
• Secondary ID: U01AI138897NIAID
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: December 6, 2021
• Est. completion date: March 4, 2025

Study information

• Verified date: March 2024
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 400
• Est. completion date: March 4, 2025
• Est. primary completion date: February 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Kidney Transplant Recipients
• Liver Transplant Recipients

Intervention

Biological:
• Pfizer-BioNTech COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
• Moderna COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.

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

Locations

Country	Name	City	State
United States	Emory Healthcare	Atlanta	Georgia
United States	Johns Hopkins Institute for Clinical and Translational Research: Broadway Adult Outpatient Clinical Research Unit	Baltimore	Maryland
United States	University of Illinois Health	Chicago	Illinois
United States	Northwestern University	Evanston	Illinois
United States	Houston Methodist	Houston	Texas
United States	University of Iowa Hospitals	Iowa City	Iowa
United States	University of Wisconsin-Madison	Madison	Wisconsin
United States	Ochsner Health	New Orleans	Louisiana
United States	Mt. Sinai Hospital	New York	New York
United States	NYU Langone Transplant Institute	New York	New York
United States	Weill Cornell Medicine	New York	New York
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California, San Diego	San Diego	California
United States	University of California San Francisco Health	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Johns Hopkins University, PPD

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Serum antibody titer will be measured using the Roche Elecsys®) severe acute respiratory syndrome coronavirus type 2 serological (anti-SARS-CoV-2) S assay.	Day 30 After Study Vaccination
Secondary	Frequency of Solicited Local Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 7 Post Study Vaccination
Secondary	Frequency of Solicited Local Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 7 Post Study Vaccination
Secondary	Frequency of Solicited Systemic Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 7 Post Study Vaccination
Secondary	Frequency of Solicited Systemic Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 7 Post Study Vaccination
Secondary	Frequency of Any Serious Adverse Events (SAEs)	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 30 Post Study Vaccination
Secondary	Frequency of Any Unsolicited Adverse Events (AEs)	Safety measure. An AE associated with the receipt of the study's COVID-19 mRNA vaccine and/or study mandated procedures.	Through Day 30 Post Study Vaccination
Secondary	Frequency of Any Serious Adverse Events (SAEs)	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 60 Post Study Vaccination
Secondary	Frequency of Any Serious Adverse Events (SAEs)	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 365 Post Study Vaccination
Secondary	Frequency of Any Unsolicited Adverse Events (AEs)	Safety measure. An AE associated with the receipt of of the study's COVID-19 mRNA vaccine and/or study mandated procedures.	Through Day 365 Post Study Vaccination
Secondary	Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection	Safety measure post receipt of the study's COVID-19 mRNA vaccine.	Through Day 60 Post Study Vaccination
Secondary	Proportion of Participants who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 60 Post Study Vaccination
Secondary	Proportion of Participants with Graft Loss	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 60 Post Study Vaccination
Secondary	Occurrence of Death Among Participants	Safety measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 60 Post Study Vaccination
Secondary	Frequency of Positive SARS-CoV-2 Test Results Using Real-Time Polymerase Chain Reaction (RT-PCR)	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.	Baseline (Day 0, Prior to Study Vaccination), Month 1, 3, 6, 9 and 12
Secondary	Occurrence of Symptomatic COVID-19	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 365 Post Study Vaccination
Secondary	Occurrence of COVID-19 Requiring Hospitalization	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.	Through Day 365 Post Study Vaccination
Secondary	Change from Baseline in Anti-SARS-CoV-2 Antibody Levels at Day 30	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.	Baseline (Day 0, Prior to Study Vaccination),Day 30 After Study Vaccination
Secondary	Change from Baseline in SARS-CoV-2 Antibody Levels	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.	From Baseline (Day 0, Prior to Study Vaccination) to Day 365 Post Study Vaccination
Secondary	Fold Increase in SARS-CoV-2 Antibody Levels: Limited to Participants With Detectable Antibody Levels at Baseline (Day 0)	Efficacy measure after receipt of the study's COVID-19 mRNA vaccine.	Baseline (Day 0, Prior to Receipt of COVID-19 Study Vaccination), Day 30 After Study Vaccination

External Links

•   National Institute of Allergy and Infectious Diseases