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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 29
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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:
- Receive a study dose of mRNA based COVID-19 vaccine (booster) with no change in their immunosuppressive regimen, or
- 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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Individuals who meet all the following criteria are eligible for enrollment as study participants-
- •Able to understand and provide informed consent
- •Individual ≥18 years of age.
- •Recipient of a kidney or liver transplant ≥12 months prior to enrollment, without allograft rejection in the 6 months preceding enrollment
- •Negative for anti-donor human leukocyte antigens (HLA) antibodies at screening (Central Lab Test Determination).
- •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
- •Received a minimum of 3 doses of either the Moderna coronavirus infectious disease 19 (COVID-19) vaccine or Pfizer-BioNTech COVID-19 vaccine
- •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.
- •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.
- •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.
排除标准
- •Individuals who meet any of these criteria are not eligible for enrollment as study participants-
- •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
- •Recipient of any allograft other than a kidney or liver
- •Participant is pregnant
- •Any past history of Donor Specific Antibody (DSA) using local site standards
- •Prior receipt of the Moderna COVID-19 Vaccine 2023-2024 or Pfizer-BioNTech COVID-19 Vaccine 2023-
- •Currently taking any systemic immunosuppressive agent, other than their prescribed transplant immunosuppression
- •Known history of severe allergic reaction to any component of an authorized or licensed COVID-19 vaccine
- •Thrombotic events, myocarditis, or pericarditis temporally associated with a prior dose of COVID-19 vaccine
- •History of heparin-induced thrombocytopenia
- •Any change in transplant immunosuppression regimen (drug or dose) in response to suspected or proven rejection within the last 6 months
- •More than minimal graft dysfunction, in accordance with study definition
- •Receipt of any cellular depleting agent (e.g. antithymocyte globulins (ATG), rituximab, alemtuzumab, Cyclophosphamide) within 12 months preceding enrollment
- •Concurrent autoimmune disease at risk for exacerbation with immunosuppression reduction
- •Any untreated active infection including BK viremia >10^4 copies
- •Infection with human immunodeficiency virus (HIV)
- •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)
- •Treatment or prophylaxis of COVID-19 with a monoclonal antibody product or convalescent plasma within 6 months preceding enrollment, or
- •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.
研究组 & 干预措施
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
干预措施: Pfizer-BioNTech COVID-19 Vaccine 2023-2024 (Biological)
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
干预措施: SOC IS Regimen (Drug)
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
干预措施: Pfizer-BioNTech COVID-19 Vaccine 2023-2024 (Biological)
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
干预措施: SOC IS Reduction (Drug)
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
干预措施: Moderna COVID-19 Vaccine 2023-2024 (Biological)
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
干预措施: SOC IS Regimen (Drug)
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
干预措施: Moderna COVID-19 Vaccine 2023-2024 (Biological)
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
干预措施: SOC IS Reduction (Drug)
结局指标
主要结局
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.
时间窗: 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.
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.
时间窗: 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.
次要结局
- 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)
- Occurrence of Symptomatic COVID-19(Through Day 365 Post Study Vaccination)
- Occurrence of COVID-19 Requiring Hospitalization(Through Day 365 Post Study Vaccination)
- 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)
- Frequency of Any Serious Adverse Events (SAEs)(Through Day 365 Post Study Vaccination)
- Frequency of Any Unsolicited Adverse Events (AEs)(Through Day 365 Post Study Vaccination)
- Proportion of Participants Treated for Acute Cell-Mediated and/or Antibody-Mediated Allograft Rejection(Through Day 60 Post Study Vaccination)
- Proportion of Participants who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody(Through Day 60 Post Study Vaccination)
- Proportion of Participants with Graft Loss(Through Day 60 Post Study Vaccination)
- Change from Baseline in SARS-CoV-2 Antibody Levels(From Baseline (Day 0, Prior to Study Vaccination) to Day 365 Post Study Vaccination)
- 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)
- Frequency of Solicited Local Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine(Through Day 7 Post Study Vaccination)
- Frequency of Solicited Systemic Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine(Through Day 7 Post Study Vaccination)
- Frequency of Solicited Local Reactogenicity Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine(Through Day 7 Post Study Vaccination)
- Frequency of Solicited Systemic Allergic Reaction Adverse Events (AEs) to the mRNA-Based COVID-19 Vaccine(Through Day 7 Post Study Vaccination)
- Occurrence of Death Among Participants(Through Day 60 Post Study Vaccination)
- Proportion of Participants With Local Solicited Adverse Reactions Within 7 Days After Additional Vaccine Dose(Through Day 7 post Vaccine dose)
- Proportion of Participants With Systemic Solicited Adverse Reactions Within 7 Days After Additional Vaccine Dose(Through Day 7 post Vaccine dose)
- Proportion of Participants With Solicited Potential Allergic Reactions Within 7 Days After Additional Vaccine Dose(Through Day 7 post Vaccine dose)
- Frequency of Any Serious Adverse Events (SAEs) During the 30 Days Following the Additional Dose of Vaccine(Through Day 30 Post Study Vaccination)
- Proportion of Participants Who Develop de Novo Donor-Specific Anti-Human Leukocyte Antigens (HLA) Antibody(Through Day 90 Post Study Vaccination)
- Proportion of Participants With Graft Loss(Through Day 60 Post Study Vaccination)
- 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)
- Change From Baseline in SARS-CoV-2 Antibody Levels(From Baseline (Day 0, Prior to Study Vaccination) to Day 365 Post Study Vaccination)
- 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)
- Frequency of Any Serious Adverse Events (SAEs)(Through Day 30 Post Study Vaccination)
- Frequency of Any Unsolicited Adverse Events (AEs)(Through Day 30 Post Study Vaccination)
- Frequency of Any Serious Adverse Events (SAEs)(Through Day 60 Post Study Vaccination)