FVIII Point-of-Care Monitoring Device and App

FVIII 护理点监控设备和应用程序

• 批准号: 10261347
• 负责人: Eugene Yan-ho Chan
• 金额: $ 72.47万
• 依托单位: DNA MEDICINE INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-10 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10261347
• 关键词: Adult; Affect; Anticoagulants; Automation; Benchmarking; Bilirubin; Biological Assay; Birth; Blood; Blood capillaries; Blood specimen; Bluetooth; Boston; Caregivers; Child; Citrates; Clinical; Coagulation Process; Computer software; Consent; Data; Devices; Disease; Dose; Drug Kinetics; Effectiveness; Engineering; Ensure; F8 gene; Fluorogenic Substrate; Freeze Drying; Genetic Diseases; Goals; Gold; Half-Life; Hand; Head; Hematocrit procedure; Hemoglobin; Hemophilia A; Hemorrhage; Heparin; Home; Human; Incidence; Individual; Infusion procedures; Institutes; Institutional Review Boards; Intervention; Interview; Joints; Laboratories; Laboratory Personnel; Lead; Link; Lupus Coagulation Inhibitor; Manuals; Measurement; Measures; Medical; Methods; Monitor; Patient Care; Patients; Pediatric Hospitals; Performance; Pharmaceutical Preparations; Phase; Physical activity; Plasma; Process; Protocols documentation; Provider; Reagent; Recombinants; Recovery; Risk; Running; Sampling; Self Assessment; Site; Standardization; Testing; Therapeutic; Time; Translating; Triglycerides; United States National Aeronautics and Space Administration; Variant; Venous; Video Recording; Whole Blood; Work; base; care providers; cost effective; dosage; gene therapy; inhibitor/antagonist; innovation; laboratory equipment; male; monitoring device; novel therapeutics; point of care; point-of-care diagnostics; precision medicine; prototype; recessive genetic trait; recruit; success; trend

FVIII Point-of-Care Monitoring Device and App Summary/Abstract Hemophilia A results from a deficiency of FVIII-activity and can result in severe bleeding. Head bleeds can be debilitating and joint-bleeds require major medical intervention. In this Direct-to-Phase II effort, we will leverage our CE-marked FVIII fluorogenic substrate assay to develop a cost-effective point-of-care (POC) FVIII test for whole venous or capillary blood with a 15-minute turnaround time. Hemophilia A is an X-linked recessive genetic disorder with an incidence of 1 in 5000 live male births. For patients with hemophilia A, lifelong treatment is required to provide adequate and therapeutic FVIII levels. The ability to monitor their FVIII levels is essential to maintaining optimal therapeutic dosing. Individual pharmacokinetics can affect the clearance of recombinant FVIII therapies. Over time, patients can develop inhibitors, which may dramatically change a drug’s effectiveness over time. Given, the complexity of FVIII lab measurements, there are currently no FVIII measurement approaches available at the point-of-care. All approaches to FVIII measurements are reliant on skilled clinical laboratory personnel and specialized laboratory equipment for assay automation, resulting in challenges to standardization, implementation, and access. In preliminary work, we have developed three innovations: (1) a high-sensitivity CE-marked FVIII fluorogenic assay that spans < 1 -200% FVIII levels, (2) a sample-to-answer capable cartridge that performs all sample processing for our assay, and (3) a concept FVIII prototype device and app wireframe. In this proposed work, we plan to leverage our work to advance FVIII monitoring work via three aims: (1) Demonstrate a CLIA-waivable sample-to-answer consumable, (2) Assess our FVIII monitoring device, app, and consumable performance over 1-200 FVIII% levels, with interfering substances, and on capillary blood, (3) Assess FVIII monitoring device at Boston Children’s Hospital (N=45) on hemophilia patients, study human factors and precision. During the effort, we will work closely with hemophilia experts, including the World Federation of Hemophilia, to ensure we have an approach for all patients worldwide. The success of developing a FVIII POC diagnostic will allow patients and providers a precision medicine approach to managing their disease. Home use will allow for more frequent measurement of FVIII levels to ensure therapeutics levels prior to engaging in physical activity and to assess correct dosage administration, including potential missed doses. It will allow newer therapies, including extended half-life PEGylated FVIII and gene therapies, to be monitored. The approach can be utilized to create FVIII activity trends which can be translated into pK data to assess changes over time, which may alert care providers to test for inhibitors. The results of our efforts will be a human-centered FVIII Bluetooth-connected monitoring device, consumable, and app that will provide accurate and easy FVIII monitoring with the goals of decreasing risk of unexpected bleeding and increasing patient care in all settings.

FVIII 护理点监控设备和应用程序 摘要/摘要 A 型血友病是由 FVIII 活性缺乏引起的，可导致严重出血。头流血 可能会使人衰弱，关节出血需要重大医疗干预。在这项直接进入第二阶段的工作中，我们 将利用我们带有 CE 标记的 FVIII 荧光底物测定来开发具有成本效益的护理点 (POC) 全静脉或毛细血管血的 FVIII 测试，周转时间为 15 分钟。 A 型血友病是 一种 X 连锁隐性遗传病，其发病率为五千分之一的活产男婴。对于患有以下疾病的患者 对于 A 型血友病，需要终身治疗才能提供足够的治疗性 FVIII 水平。有能力 监测 FVIII 水平对于维持最佳治疗剂量至关重要。个体药代动力学 可能会影响重组 FVIII 疗法的清除率。随着时间的推移，患者会产生抑制剂，这可能 随着时间的推移，药物的有效性会发生巨大的变化。鉴于 FVIII 实验室测量的复杂性， 目前尚无可用于现场护理的 FVIII 测量方法。 FVIII 的所有方法 测量依赖于熟练的临床实验室人员和专门的实验室设备 检测自动化，给标准化、实施和访问带来挑战。 在前期工作中，我们开发了三项创新：(1) 具有 CE 标志的高灵敏度 FVIII 荧光检测，跨度 < 1 -200% FVIII 水平，(2) 具有从样本到答案的能力的试剂盒， 执行我们测定的所有样品处理，以及 (3) 概念 FVIII 原型设备和应用程序 线框。在这项拟议的工作中，我们计划利用我们的工作通过三个方面推进 FVIII 监测工作 目标：(1) 展示可免除 CLIA 的样品到答案消耗品，(2) 评估我们的 FVIII 监测 设备、应用程序和耗材性能超过 1-200 FVIII% 水平（存在干扰物质） 毛细血管血，(3) 评估波士顿儿童医院 (N=45) 的 FVIII 监测装置对血友病的影响 患者，研究人为因素和精度。在此过程中，我们将与血友病专家密切合作， 包括世界血友病联合会，以确保我们为全世界所有患者提供治疗方法。 FVIII POC 诊断的成功开发将使患者和提供者能够精确地 医学方法来管理他们的疾病。家庭使用将允许更频繁地测量 FVIII 水平，以确保在进行身体活动之前的治疗水平并评估正确的剂量 给药，包括潜在的漏服剂量。它将允许更新的疗法，包括延长半衰期 聚乙二醇化 FVIII 和基因疗法，待监测。该方法可用于创建 FVIII 活性 趋势可以转化为 pK 数据以评估随时间的变化，这可能会提醒护理人员 抑制剂测试。我们努力的成果将是一个以人为本的FVIII蓝牙连接监控 设备、耗材和应用程序将提供准确、轻松的 FVIII 监测，以减少 意外出血的风险并增加所有环境下的患者护理。