Clinical Trial of the FAST Real-Time GFR System

描述(申请人提供)：Pharmaco Photonics(DBA FAST，Inc.)建议在其首个人类先导研究中进行快速跟踪研究以确定GFR。该SBIR项目的长期目标是在人体上测试FAST的基于导管的微创荧光设备，并将该设备商业化，以便对急性肾脏损伤(AKI)和/或慢性肾脏疾病(CKD)患者的肾小球滤过率(GFR)进行快速检测和量化。AKI仍然是一个令人头疼的临床问题，导致不可接受的高死亡率、慢性肾脏病的发展和终末期肾脏疾病的加速进展。FAST公司开发了FAST GFR系统TM，这是一种用于直接测量GFR的微创技术。在CKD患者中，用于确定基线GFR以及跟踪疾病进展和治疗反应的估计GFR(EGFR)方法已被证明令人失望。拥有快速测量GFR(MGFR)的能力将极大地改善患者的分层、管理和治疗评估。该系统旨在作为目前用于评估肾功能的方法的补充。该系统已经成功地在狗的生理和AKI条件下进行了测试，并显示出与GFR的研究金标准测量密切相关。在这一成功的基础上，FAST建议在FDA-研究设备豁免(IDE)试点人体试验(A)下，在人体上测试FAST GFR System TM设备(第一阶段特定目标1)，以确定GFR和血浆容量。将在八(8)名健康志愿者身上测定GFR，以便与碘海醇清除剂相比评估系统的安全性和有效性，建立人体剂量和测试参数，并评估静脉注射可视荧光注射剂的药代动力学特征。在第一阶段取得成功的基础上，FAST将在FDA-IDE下测试FAST GFR系统TM，以确定GFR和血浆容量，进行第二阶段特定目标1的试点人体试验(B)。GFR将在包括AKI在内的各种肾脏损伤的总共24(24)名受试者中进行测定，以便对肾脏疾病中所见的GFR的范围进行安全性和有效性的评估。这种快速的GFR SystemTM方法对AKI和CKD患者具有重要的临床意义，特别是在高危患者中，这些患者需要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，这项快速测量GFR的新技术将首次允许在人类疾病的多种动物模型中对肾功能进行早期动态评估；从而扩大关于肾功能在疾病早期发病过程中的作用的科学知识。

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.