FVIII Point-of-Care Monitoring Device and App

FVIII床旁监测设备和应用程序 摘要/摘要 血友病A是由FVIII活性缺乏引起的，可导致严重出血。头部出血 可能会使人虚弱，关节出血需要主要的医疗干预。在这直接到第二阶段的努力，我们 将利用我们的CE标记的FVIII荧光底物检测来开发具有成本效益的床旁检测 (POC)全静脉血或毛细血管血的FVIII检测，周转时间为15分钟。血友病A是 一种X连锁隐性遗传疾病，发病率为1/5000活产男婴。患者 血友病A，需要终身治疗，以提供足够的和治疗性的FVIII水平。的能力 监测其FVIII水平对于维持最佳治疗剂量至关重要。个体药代动力学 可影响重组FVIII治疗的清除。随着时间的推移，患者可能会产生抑制剂， 会随着时间的推移显著改变药物的有效性。鉴于FVIII实验室测量的复杂性， 目前在床旁没有可用的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， 分析自动化，导致对标准化、实施和访问的挑战。 在前期工作中，我们开发了三项创新：（1）高灵敏度CE标志 FVIII荧光测定，其跨越< 1 - 200%FVIII水平，（2）能够进行样品-应答的盒，其 为我们的检测执行所有样本处理，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，我们计划通过三个方面利用我们的工作来推进FVIII监测工作。 目的：（1）展示CLIA豁免的样本到答案消耗品，（2）评估我们的FVIII监测 器械、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）FVIII监测装置对血友病的影响 患者，研究人为因素和精度。在努力过程中，我们将与血友病专家密切合作， 包括世界血友病联合会，以确保我们为全球所有患者提供一种方法。 开发FVIII POC诊断的成功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，以确保在从事体力活动之前的治疗水平，并评估正确的剂量 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 监测PEG化FVIII和基因治疗。该方法可用于产生FVIII活性 可转化为pK数据的趋势，以评估随时间的变化，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一个以人为中心的FVIII蓝牙连接监测 设备、耗材和应用程序，可提供准确、简便的FVIII监测， 意外出血的风险，并在所有情况下增加患者护理。

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.