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.

实体器官移植患者因新冠肺炎感染死亡率较高，原因是 免疫抑制和合并症。尽管SARS-CoV-2疫苗接种在全球范围内非常有效 普通人群，最近的研究表明，实体器官移植的接受者不太可能发生 保护性抗体反应。此外，长期的安全性研究，包括免疫后遗症，如 缺乏排斥反应和新的供体特异性抗体的形成。 我们提出了一项多中心随机适应性设计试验来研究Cpat(COVID)的策略 移植后的保护)。这项试验将基于CPAT在200例肾移植中的先导试验的结果 将研究第三剂SARS-CoV-2mRNA疫苗在中国的安全性和免疫原性的研究 在标准的2剂剂量系列后未能产生高水平抗体的受者。这场审判将确定关键 风险和疗效的相关性。这项试验将结合这些数据来调查额外的保护策略 包括不同疫苗平台的使用和800固体器官中免疫抑制的变化 在15个美国移植中心，移植受者的抗尖峰抗体反应不佳。这场审判 将使用贝叶斯对具有最高成功概率的候选手臂进行个性化随机化 框架。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免疫。 我们的多学科团队包括移植外科、传染病、流行病学、 生物统计学、病理学、病毒学和免疫学。我们的团队有成功招生和 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 在全美800名移植受者中采用新的SARS-CoV-2疫苗接种策略。重要 机制研究将进一步加深对保护性免疫反应发展的基本理解 这些脆弱的人群。