Clinical and Non-Clinical Evaluations of repeat administrations of the FAST PV and mGFR Technology

FAST PV 和 mGFR 技术重复给药的临床和非临床评估

• 批准号: 9148189
• 负责人: Daniel Meier
• 金额: $ 99.94万
• 依托单位: PHARMACOPHOTONICS, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-20 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9148189
• 关键词: Acute; Acute Renal Failure with Renal Papillary Necrosis; Adopted; Animal Model; Blood; Blood Plasma Volume; Canis familiaris; Caring; Chronic Kidney Failure; Clinical; Clinical Research; Creatinine; Critical Care; Data; Development; Devices; Diagnosis; Disease Progression; Dose; Early Diagnosis; End stage renal failure; Equation; Equilibrium; Evaluation; Fluorescence; Funding; Glomerular Filtration Rate; Goals; Health; Hour; Human; Injury; Intensive Care Units; Iohexol; Iothalamate; Kidney; Kidney Diseases; Kidney Function Tests; Knowledge; Legal patent; Life; Literature; Marketing; Measurement; Measures; Methodology; Methods; Morbidity - disease rate; Onset of illness; Patients; Performance; Pharmaceutical Preparations; Phase; Physicians; Physiological; Proteins; Radioactivity; Rattus; Renal function; Reporter; Reproducibility; Research; Role; Safety; Serum; Severities; Signal Transduction; Small Business Innovation Research Grant; Stratification; Structure; Techniques; Technology; Testing; Therapy Evaluation; Time; Toxicology; Translations; Variant; Venous; base; clinical application; healthy volunteer; high risk; human disease; human subject; improved; mathematical algorithm; mortality; new technology; patient stratification; photonics; point of care; pre-clinical; preclinical study; rapid detection; research clinical testing; response; safety testing; success; urinary; volunteer

 DESCRIPTION (provided by applicant): Pharmaco Photonics (DBA FAST Biomedical) proposes a PHASE IIB project to determine the safety and functionality of repeat administration of the FAST PV and mGFR Technology in both non-clinical and clinical studies. The long-term goal of this SBIR project is to test FAST's fluorescent based test in humans and commercializes this product for rapid detection and quantification of glomerular filtration rate (GFR) and plasma volume (PV) in patients with acute kidney injury (AKI) chronic kidney disease (CKD), and/or volume instability. 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 PV and mGFR Technology, a simple blood draw technique for direct measurement of GFR and PV. 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 Test is intended as an adjunct to current methods utilized to assess renal function. This Test has been successfully tested under physiologic and AKI conditions in dogs and in increasing levels of CKD in humans. Based upon this success, FAST proposes to test the repeated administration of the FAST PV and mGFR Technology TM in repeat dose non-clinical studies (Phase IIB Specific Aim 1). Based on success of the non-clinical studies FAST proposes to test the repeated administration of the FAST PV and mGFR Technology TM in humans (Phase IIB Specific Aim 2) for determination of GFR and PV, under an FDA- Investigational Device Exemption (IDE) Pilot Human Trial (C). GFR and PV will be determined in sixteen (16) healthy volunteers receiving either a volume (8) or protein (8) challenge in order to evaluate the test's safety with rapid repeated doses, efficacy, and repeatability and quantify renal reserve. It will also be studied in an additional eight (8) volunteers of varying degrees of kidney function and compared to an iothalamate clearance with both repeated one week later. This will allow for the evaluation of safety and efficacy over the spectrum of GFRs seen in kidney disease, with repeat doses one week apart and compared to the present day standard. This FAST PV and mGFR Technology TM 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. Finally, the ability to quantify and follow PV dynamically will greatly aid the critical care physician in many ICU patients.

 描述(由申请人提供)：Pharmaco Photonics(DBA FAST Biomedical)提出了一个IIB阶段项目，以确定在非临床和临床研究中重复使用FAST PV和mGFR技术的安全性和功能性。这一SBIR项目的长期目标是在人类身上测试FAST的基于荧光的测试，并将该产品商业化，用于对急性肾损伤(AKI)、慢性肾脏疾病(CKD)和/或容量不稳定患者的肾小球滤过率(GFR)和血浆容量(PV)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开发了FAST PV和mGFR技术，这是一种直接测量GFR和PV的简单抽血技术。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。该测试旨在作为目前用于评估肾功能的方法的补充。这项测试已经成功地在狗的生理和AKI条件下进行了测试，并在人类中增加了CKD的水平。在这一成功的基础上，FAST建议在重复剂量的非临床研究中测试FAST PV和mGFR技术TM的重复给药(IIB阶段特定目标1)。基于非临床研究的成功，FAST建议在FDA-研究设备豁免(IDE)试点人体试验(C)下，测试在人类身上重复使用FAST PV和mGFR Technology TM(IIB特定目标2)以确定GFR和PV的情况。GFR和PV将在接受容量(8)或蛋白质(8)挑战的16名健康志愿者中进行测定，以评估快速重复剂量试验的安全性、有效性和重复性，并量化肾脏储备。它还将在另外八(8)名不同程度肾功能的志愿者身上进行研究，并与一周后两者都重复的异硫氰酸酯清除进行比较。这将允许在肾脏疾病中看到的GFRs的频谱上评估安全性和有效性，重复剂量间隔一周，并与当今的标准进行比较。这种快速的PV和mGFR技术TM对AKI和CKD患者具有重要的临床意义，特别是在需要进行严密监测以进行早期诊断、按严重程度分层和治疗反应的高危患者中。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。最后，量化和动态跟踪PV的能力将大大 帮助许多ICU患者的重症监护医生。