Late stage development and preparation of a long-term non-enzymatic continuous glucose sensor for clinical trials

摘要 糖尿病是一种复杂的多因素疾病，它会缩短受影响个人的生活时间和生活质量。 连续血糖监测仪(CGM)的使用对于患有以下疾病的患者来说是一种宝贵的管理工具 这种慢性且代价高昂的疾病。然而，尽管经过多年的发展，目前可获得的连续葡萄糖 监护仪(CGM)对于糖尿病的短期使用，特别是长期使用，仍然缺乏良好的准确性和可靠性 管理层。实现长期、准确的CGM的主要障碍是传感器的不稳定性 化学和身体对传感器的免疫反应--特别是异物反应(FBR)-- 导致生物污垢、炎症、无血管纤维化和感应化学降解。此外，当前 市场上和正在开发中的CGM系统要么是笨重的经皮探头，要么是可植入的 包裹在硬金属或塑料中的装置，随着时间的推移或被无血管组织囊包围 被免疫细胞吸收(如果是纳米大小的话)。普罗夫萨已经开发出荧光、非酶的硼酸 (BA)基于葡萄糖传感器，以组织整合水凝胶的形式生产，已被证明 最大限度地减少FBR，实现长期监控。在这个CRP SBIR中，我们的目标是成功地引导我们的 通过后期开发和至关重要的技术活动展示了可注射葡萄糖传感器 为了商业化。这项技术的临床转化将激励和实现糖尿病和糖尿病前期 患者更严格地控制血糖水平，不用担心低血糖，会减少糖尿病 医疗系统的疾病负担。在这个项目中，我们建议为第一个人类做好准备 临床试验，作为迈向商业化的第一步。为此，我们将示范生产无菌， 生物兼容的封装传感器可用于临床试验，以确保符合法规 标准。我们将进行市场调查分析，以确定目标人群，评估报销情况 潜力，并制定监管战略，使临床开发与业务目标保持一致。此外, 我们将完成有关调查设备豁免的文件。最后，我们将设计和规划 一项首例人类(FIH)临床试验，为IRB提交准备所有必要的文件。这项提议将 帮助Prousa将其葡萄糖传感器推向商业化，以显著改善健康和 糖尿病前期和糖尿病患者的生活质量。

Abstract Diabetes is a complex multi-factorial disease that diminishes the length and quality of life of affected individuals. The use of continuous glucose monitors (CGM) can be an invaluable management tool for patients afflicted by this chronic and costly disease. However, despite years of development, currently available continuous glucose monitors (CGMs) still lack good accuracy and reliability for short-term and particularly, long-term use in diabetes management. The main obstacles to achieving a long-term, accurate CGM are instabilities in the sensing chemistry and the body’s immune response against the sensor – specifically the foreign body response (FBR) – leading to biofouling, inflammation, avascular fibrosis and sensing chemistry degradation. Additionally, current CGM systems in the market and under development are either bulky percutaneous probes or implantable devices encased in hard metals or plastics that become surrounded by an avascular tissue capsule over time or are taken up by immune cells (if nano-sized). Profusa has developed fluorescent, non-enzymatic boronic acid (BA)-based glucose sensors that are produced in a tissue-integrating hydrogel format that has been shown to minimize the FBR, enabling long-term monitoring. In this CRP SBIR, we aim to guide our successfully demonstrated injectable glucose sensors through late stage development and technical activities that are vital for commercialization. Clinical translation of this technology will motivate and enable diabetic and pre-diabetic patients to more tightly control their glucose levels without fear of hypoglycemia and will reduce the diabetes disease burden on the healthcare system. In this project, we propose to prepare the path for first-in-human clinical testing, as a first step towards commercialization. To this end, we will demonstrate production of sterile, biocompatible, packaged sensors ready for clinical trial use in order to ensure compliance with regulatory standards. We will perform market research analysis to determine target population, assess reimbursement potential, and develop regulatory strategies to align clinical development with business objectives. In addition, we will complete documentation regarding investigational device exemption. Finally, we will design and plan for a first-in-human (FIH) clinical trial by preparing all necessary documents for IRB submission. This proposal will aid Profusa in moving its glucose sensor towards commercialization, to significantly improve the health and quality of life of pre-diabetic and diabetic patients.