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 血友病A来自FVIII-ATIVITIVE的缺乏，可能导致严重的出血。头流血 可以使人衰弱，而联合人需要进行大量的医疗干预。在这一直接到相之间的努力中，我们 将利用我们的CE标记的FVIII荧光底物分析来开发具有成本效益的护理 （POC）FVIII测试全静脉或毛细血管血液，其周转时间为15分钟。血友病A是 X连锁的隐性遗传疾病，有5000名活着的男性出生中有1例。适用于患者 血友病A，终身治疗需要提供足够的治疗性FVIII水平。能力 监测其FVIII水平对于维持最佳治疗剂量至关重要。单个药代动力学 会影响重组FVIII疗法的清除。随着时间的流逝，患者可以发展抑制剂，这可能 随着时间的流逝，数字上会改变药物的有效性。给出了FVIII实验室测量的复杂性 目前尚无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 测定自动化，导致标准化，实施和访问的挑战。 在初步工作中，我们开发了三个创新：（1）高敏性CE标记 FVIII荧光测定法，跨越<1 -200％的FVIII水平，（2）样品与撤离的墨盒 为我们的评估执行所有样本处理，（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来通过三个 目的：（1）演示可消耗的Clia-Waiver样品到答案，（2）评估我们的FVIII监测 设备，应用程序和可消耗性能超过1-200个FVIII％水平，具有干扰物质， 毛细血管血，（3）评估波士顿儿童医院的FVIII监测装置（n = 45） 患者，研究人为因素和精度。在努力中，我们将与血友病专家紧密合作， 包括世界血友病联合会，以确保我们在全球所有患者中都有一种方法。 开发FVIII POC诊断的成功将使患者和提供者精确 治疗疾病的医学方法。家庭用途将允许更频繁地测量FVIII 在进行体育锻炼之前确保治疗水平的水平并评估正确的剂量 管理，包括潜在的错剂量。它将允许更新的疗法，包括延长的半衰期 要监测的FVIII和基因疗法。该方法可以用于创建FVIII活动 可以将可以转化为PK数据以评估随着时间的变化的趋势，这可能会提醒护理提供者 测试抑制剂。我们努力的结果将是以人为本的FVIII蓝牙连接监测 设备，消耗量和应用程序将提供准确，简单的FVIII监视，并具有减少的目标 在所有情况下，出现意外出血并增加患者护理的风险。