COVID Protection After Transplant (CPAT) Multicenter Adaptive Trial

移植后新冠肺炎保护 (CPAT) 多中心适应性试验

• 批准号: 10457200
• 负责人: Christine Marie Durand
• 金额: $ 694.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10457200
• 关键词: 2019-nCoV; Acute; Adenovirus Vector; Adjuvant; Antibodies; Antibody Formation; Antibody Response; Antigens; Antimetabolites; Avidity; B-Lymphocyte Subsets; Bayesian Modeling; Biological Assay; Biometry; CD8-Positive T-Lymphocytes; COVID-19; COVID-19 mortality; COVID-19 pandemic; COVID-19 vaccination; COVID-19 vaccine; Cellular Immunity; Coupled; Data; Development; Diabetes Mellitus; Dose; Effectiveness; Enrollment; Epitopes; Event; Flow Cytometry; Functional disorder; Futility; General Population; Goals; Heart; Humoral Immunities; Immune response; Immunity; Immunocompetent; Immunodominant Epitopes; Immunoglobulin Class Switching; Immunologic Memory; Immunologics; Immunology; Immunophenotyping; Immunosuppression; Infection; Infectious Disease Epidemiology; Infrastructure; Intervention; Kidney; Kidney Transplantation; Libraries; Liver; Longitudinal Studies; Lung; Memory B-Lymphocyte; Messenger RNA; Metabolic; Monitor; Multi-Institutional Clinical Trial; Organ; Organ Transplantation; Pathology; Patients; Peptides; Persons; Phenotype; Pilot Projects; Population; Probability; Prospective cohort; RNA vaccine; Randomized; Reaction; Reporting; Risk; Route; Safety; Secondary Immunization; Series; Solid; Speed; Stains; T cell receptor repertoire sequencing; T cell response; Technology; Time; Transplant Recipients; Transplantation; Transplantation Surgery; United States; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Virus; Virus-like particle; Vulnerable Populations; antigen-specific T cells; arm; comorbidity; coronavirus disease; data management; design; donor-specific antibody; enzyme linked immunospot assay; experience; follow-up; immunogenic; immunogenicity; immunoregulation; improved; interest; mortality; multidisciplinary; novel; older patient; operation; pilot trial; programs; response; safety study; single-cell RNA sequencing; success; transplant centers; treatment arm; trial design; vaccination strategy; vaccine safety; vaccine trial; variants of concern; virology

Solid organ transplant recipients experience high mortality from COVID-19 due to a combination of immunosuppression and comorbidities. Although SARS-CoV-2 vaccination has been highly effective in the general population, recent studies show that solid organ transplant recipients are less likely to develop protective antibody responses. In addition, long term studies of safety, including immunologic sequela such as rejection, and de novo donor-specific antibody formation are lacking. We propose a Multicenter Randomized Adaptive Design Trial to investigate strategies for CPAT (COVID Protection After Transplant). This trial will build on results from a CPAT Pilot Trial in 200 kidney transplant reipients which will investigate the safety and immunogenicity of 3rd dose of a SARS-CoV-2 mRNA vaccines in recipients who fail to develop high level antibodies after a standard 2 dose series. That trial will identify key correlates of risk and efficacy. This trial will incorporate that data to investigate additional protective strategies including the use of different vaccine platforms and changes in immunosuppression in 800 solid organ transplant recipients with suboptimal anti-spike antibody responses across 15 US transplant centers. This trial will personalize randomization to candidate arms with the highest probability of success using a Bayesian framework. In conjuction, we will perform novel, comprehensive virologic and immunologic mechanistic studies to better understand vaccine-associated immunity over time. Our multidisciplinary team includes experts in Transplant Surgery, Infectious Diseases, Epidemiology, Biostatistics, Pathology, Virology, and Immunology. Our team has experience successfully enrolling and conducting multicenter transplantation trials (U01AI134591, U01AI138897) and will leverage existing infrastructure for operations, data management, analysis, and safety reporting. In summary, this Multicenter Adaptive Design CPAT Trial will determine the immunogenicity and safety of novel SARS-CoV-2 vaccination strategies in 800 transplant recipients across the United States. Important mechanistic studies will further fundamental understanding of development of protective immune responses in this vulnerable population.

由于以下因素的综合作用，实体器官移植受者因 COVID-19 死亡率很高 免疫抑制和合并症。尽管 SARS-CoV-2 疫苗接种在 一般人群，最近的研究表明实体器官移植受者不太可能发展 保护性抗体反应。此外，安全性的长期研究，包括免疫学后遗症，例如 排斥反应和从头形成供体特异性抗体的情况都缺乏。 我们提出了一项多中心随机自适应设计试验来研究 CPAT（新冠肺炎）策略 移植后的保护）。该试验将以 200 例肾移植的 CPAT 试点试验的结果为基础 接受者将研究第三剂 SARS-CoV-2 mRNA 疫苗的安全性和免疫原性 标准 2 剂量系列后未能产生高水平抗体的接受者。该试验将确定关键 风险和功效的相关性。该试验将结合这些数据来研究其他保护策略 包括不同疫苗平台的使用以及800个实体器官免疫抑制的变化 美国 15 个移植中心的抗尖峰抗体反应欠佳的移植受者。本次审判 将使用贝叶斯方法对具有最高成功概率的候选组进行个性化随机化 框架。与此同时，我们将进行新颖、全面的病毒学和免疫学机制研究 随着时间的推移，更好地了解疫苗相关的免疫力。 我们的多学科团队包括移植手术、传染病、流行病学、 生物统计学、病理学、病毒学和免疫学。我们的团队拥有成功注册和注册的经验 进行多中心移植试验（U01AI134591、U01AI138897）并将利用现有的 用于运营、数据管理、分析和安全报告的基础设施。 总之，这项多中心适应性设计 CPAT 试验将确定以下药物的免疫原性和安全性： 针对美国 800 名移植受者的新型 SARS-CoV-2 疫苗接种策略。重要的 机制研究将进一步深入了解保护性免疫反应的发展 这个弱势群体。