Clinical Trial of the FAST Real-Time GFR System

描述（由申请人提供）：PharmacoPhotonics（DBA FAST，Inc.）提出快速通道研究，以确定GFR在其第一个人类试点研究。该SBIR项目的长期目标是在人体中测试FAST的基于导管的微创荧光设备，并将该设备商业化，用于快速检测和定量急性肾损伤（阿基）和/或慢性肾病（CKD）患者的肾小球滤过率（GFR）。阿基仍然是一个令人烦恼的临床问题，导致不可接受的高患者死亡率、CKD的发展和向终末期肾病的加速进展。FAST开发了FAST GFR SystemTM，这是一种直接测量GFR的微创技术。在CKD患者中，用于确定基线GFR和疾病进展和治疗反应的估计GFR（eGFR）方法已被证明是令人失望的。具有快速测量GFR（mGFR）的护理点能力将大大改善患者分层，管理和治疗评估。该系统预期作为当前用于评估肾功能的方法的辅助工具。该系统已在犬的生理和阿基条件下成功测试，并显示与GFR的研究金标准测量密切相关。基于这一成功，FAST提议在FDA-研究器械豁免（IDE）初步人体试验（A）下，在人体中测试FAST GFR System TM器械（I期特定目标1），以测定GFR和血浆容量。将在8名健康志愿者中测定GFR，以评价与碘海醇清除率相比的系统安全性和有效性，确定人体给药和检测参数，并评价静脉注射可视荧光注射液的药代动力学特征。基于I期的成功，FAST将在II期特定目标1的初步人体试验（B）的FDA-IDE下测试FAST GFR System TM以测定GFR和血浆容量。将在总共24例具有广泛变化的肾损害（包括阿基）的受试者中测定GFR，以允许在肾脏疾病中观察到的GFR谱上评价安全性和疗效。这种FAST GFR SystemTM方法在阿基和CKD患者中具有重要的临床意义，尤其是在高风险患者中，这些患者需要进行密切监测以进行早期诊断、按严重程度分层和治疗反应。此外，这种用于快速测量GFR的新技术将首次允许在多种人类疾病动物模型中对肾功能进行早期动态评估;从而扩展了关于肾功能在早期疾病发作期间的作用的科学知识。 公共卫生相关性：肾损伤，无论是急性（阿基）还是慢性肾病（CKD），都构成了危及生命或通常使人衰弱的病症，因为文献表明，与未发生肾损伤的患者相比，发生肾损伤的所有患者的发病率和死亡率更高。FAST Diagnostics开发了一种突破性的肾功能测试[FAST GFR SystemTM]，通过提供准确、实时和即时的肾小球滤过率和血浆容量测量，提供了优于现有技术的具有临床意义的优势。这将有助于诊断，确定损伤程度，并测量阿基和慢性肾病患者对治疗的反应。它还将允许准确调整由肾脏清除的药物和那些对肾脏有潜在毒性的药物。

DESCRIPTION (provided by applicant): PharmacoPhotonics (DBA FAST, Inc.) proposes Fast-Track research to determine GFR in its first human Pilot study. The long-term goal of this SBIR project is to test FAST's minimally invasive catheter based fluorescent device in humans and commercialize this device for rapid detection and quantification of glomerular filtration rate (GFR) in patients with acute kidney injury (AKI) and/or chronic kidney disease (CKD). AKI remains a vexing clinical problem resulting in unacceptably high patient mortality, development of CKD and enhanced progression to end stage renal disease. FAST has developed the FAST GFR SystemTM, a minimally invasive technique for direct measurement of GFR. In CKD patients, the estimated GFR (eGFR) method for determining baseline GFR and following disease progression and response to therapy has proved to be a disappointment. Having a rapid point of care ability to measure GFR (mGFR) would greatly improve patient stratification, management and evaluation of therapies. The System is intended as an adjunct to current methods utilized to assess renal function. This System has been successfully tested under physiologic and AKI conditions in dogs, and shows a close correlation with a research gold standard measure of GFR. Based upon this success, FAST proposes to test the FAST GFR SystemTM device in humans (Phase I Specific Aim 1) for determination of GFR and plasma volume, under an FDA- Investigational Device Exemption (IDE) Pilot Human Trial (A). GFR will be determined in eight (8) healthy volunteers in order to evaluate system safety and efficacy as compared to iohexol clearance, establish human dosing and testing parameters, and evaluate the pharmacokinetic profile of the intravenously injected visual fluorescent injectate. Based on the success of Phase I, FAST will then test the FAST GFR SystemTM for determination of GFR and plasma volume, under an FDA-IDE for a Pilot Human Trial (B) in Phase II Specific Aim 1. GFR will be determined in a total of twenty-four (24) subjects with widely varying renal impairment, including AKI, to allow for evaluation of safety and efficacy over the spectrum of GFRs seen in kidney disease. This FAST GFR SystemTM method is of major clinical importance in AKI and CKD patients, especially in high risk patients where intense surveillance is necessary for early diagnosis, stratification by severity, and response to therapy. Furthermore, this new technology for rapid measurement of GFR will for the first time permit early dynamic assessment of kidney function in multiple animal models of human disease; thus expanding scientific knowledge regarding the role of kidney function during early disease onset. PUBLIC HEALTH RELEVANCE: Kidney injury, whether acute (AKI) or chronic kidney disease (CKD) constitutes a life- threatening or often debilitating condition, as literature demonstrates a higher morbidity and mortality rate among all patients who develop kidney injury compared to those who do not. FAST Diagnostics has developed a breakthrough kidney function test [FAST GFR SystemTM] that provides a clinically meaningful advantage over existing technology by providing an accurate, real-time and point of care measurement of glomerular filtration rate and plasma volume. This will aid in the diagnosis, determining the extent of injury, and measuring the response to therapy in both AKI and chronic kidney disease patients. It will also allow for accurate adjustment of medications cleared by the kidneys and those potentially toxic to the kidneys.