Kidney Transplant Recipients, Liver Transplant Recipients
Conditions
Keywords
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
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.
Interventions
BIOLOGICALPfizer-BioNTech COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
BIOLOGICALModerna COVID-19 Vaccine 2023-2024
Administration: One dose administered intramuscularly.
DRUGSOC IS Regimen
Participants will continue to take their prescribed immunosuppression (IS) medications without alterations in schedule and dosing, per protocol instruction.
DRUGSOC 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.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
New York University Langone Health
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The -Fold Change 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. Values \> 1 represent increase from baseline; values \< 1 represent decrease from baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Proportion of Participants With Local Solicited Adverse Reactions Within 7 Days After Additional Vaccine Dose | Through Day 7 post Vaccine dose | Safety measure after receipt of the study's COVID-19 mRNA vaccine. |
| Proportion of Participants With Systemic Solicited Adverse Reactions Within 7 Days After Additional Vaccine Dose | Through Day 7 post Vaccine dose | Safety measure after receipt of the study's COVID-19 mRNA vaccine. |
| Proportion of Participants With Solicited Potential Allergic Reactions Within 7 Days After Additional Vaccine Dose | Through Day 7 post Vaccine dose | Safety measure after receipt of the study's COVID-19 mRNA vaccine. |
| Frequency of Any Serious Adverse Events (SAEs) During the 30 Days Following the Additional Dose of Vaccine | Through Day 30 Post Study Vaccination | Safety measure after receipt of the study's COVID-19 mRNA vaccine. |
| 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 90 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. |
| Occurrence of Death Among Participants | Through Day 60 Post Study Vaccination | Safety measure after receipt of the study's COVID-19 mRNA vaccine. |
| 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. |
| 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 Change in SARS-CoV-2 Antibody Levels: Limited to Participants With Detectable Antibody Levels at Baseline (Day 0). (Values > 1 Represent an Increase From Baseline; Values < 1 Represent a Decrease From Baseline). | 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. |
Countries
United States
Contacts
STUDY_CHAIRDorry L. Segev, MD, PhD
Transplant Surgery, Johns Hopkins University School of Medicine
STUDY_CHAIRPeter S. Heeger, MD
Translational Transplant Research Center, Icahn School of Medicine at Mount Sinai
STUDY_CHAIRChristian P. Larsen, MD, DPhil
Emory Transplant Center, Emory University School of Medicine
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 62.5 years |
| Baseline Immunosuppression Tacrolimus, MMF or MPA, with/without corticosteroid | 9 Participants |
| Baseline Immunosuppression Tacrolimus only | 4 Participants |
| Baseline Immunosuppression Tacrolimus with <= 5mg prednisone or equivalent | 0 Participants |
| Organ transplanted Kidney | 13 Participants |
| Organ transplanted Liver | 5 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants |
| Race/Ethnicity, Customized Black/African American | 8 Participants |
| Race/Ethnicity, Customized Hispanic/Latino ethnicity | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 22 Participants |
| Region of Enrollment United States | 18 participants |
| Sex/Gender, Customized Female | 16 Participants |
| Sex/Gender, Customized Male | 12 Participants |
| Years since transplant | 3.9 Years |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 18 | 0 / 14 |
| other Total, other adverse events | 6 / 18 | 12 / 14 |
| serious Total, serious adverse events | 5 / 18 | 0 / 14 |
Outcome results
None listed