SBIR-STTR Award

FVIII Point-of-Care Monitoring Device and App Summary/ 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

Public Health Relevance Statement:
Project Narrative 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. 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.

Project Terms:
Adult; Affect; Anticoagulants; Automation; base; Benchmarking; Bilirubin; Biological Assay; Birth; Blood; Blood capillaries; Blood specimen; Bluetooth; Boston; care providers; Caregivers; Child; Citrates; Clinical; Coagulation Process; Computer software; Consent; cost effective; Data; Devices; Disease; dosage; Dose; Drug Kinetics; Effectiveness; Engineering; Ensure; F8 gene; Fluorogenic Substrate; Freeze Drying; gene therapy; Genetic Diseases; Goals; Gold; Half-Life; Hand; Head; Hematocrit procedure; Hemoglobin; Hemophilia A; Hemorrhage; Heparin; Home environment; Human; Incidence; Individual; Infusion procedures; inhibitor/antagonist; innovation; Institutes; Institutional Review Boards; Intervention; Interview; Joints; Laboratories; laboratory equipment; Laboratory Personnel; Lead; Link; Lupus Coagulation Inhibitor; male; Manuals; Measurement; Measures; Medical; Methods; Monitor; monitoring device; novel therapeutics; Patient Care; Patients; Pediatric Hospitals; Performance; Pharmaceutical Preparations; Phase; Physical activity; Plasma; point of care; point-of-care diagnostics; precision medicine; Process; Protocols documentation; prototype; Provider; Reagent; recessive genetic trait; Recombinants; Recovery; recruit; Risk; Running; Sampling; Self Assessment; Site; Standardization; success; Testing; Therapeutic; Time; Translating; trend; Triglycerides; United States National Aeronautics and Space Administration; Variant; Venous; Video Recording; Whole Blood; Work

FVIII Point-of-Care Monitoring Device and App Summary/AbstractHemophilia 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. Public Health Relevance Statement Project Narrative 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. 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.