STTR Phase II: Advance Early Detection of Lupus Nephritis with ClearGold

STTR II 期：利用 ClearGold 推进狼疮性肾炎的早期检测

基本信息

批准号：
10494086
负责人：
Mengxiao Yu
金额：
$ 60.52万
依托单位：
CLEARNANO, INC.
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-19 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10494086
关键词：
Address Advanced Development Affect American Area Under Curve Autoimmune Diseases Biological Markers Bladder Cells Chemistry Clinic Clinical Clinical Research Clinical Trials Creatinine Cysteine Detection Diagnostic tests Disease Disease Progression Dose Early Diagnosis Early Intervention Early treatment Evaluation Event Financial Hardship Glutathione Goals Gold Grant Head Henle&apos s loop Hour Individual Injections Injury to Kidney Intravenous Investigational Drugs Iohexol Kidney Kidney Failure Kidney Transplantation LCN2 gene Lead Lupus Lupus Nephritis Measures Medical Methods Modeling Monitor Mus Names Nanotechnology Outcomes Research Particle Size Patients Performance Persons Phase Practice Guidelines Production Proteins Proteinuria ROC Curve Rattus Reaction Renal clearance function Renal dialysis Risk Rivers Small Business Technology Transfer Research Spottings Sprague-Dawley Rats Staging Surface Systemic Lupus Erythematosus Technology Testing Toxic effect Toxicology Translating Tumor-infiltrating immune cells Urine acute toxicity base biomaterial compatibility clinical translation disorder prevention early detection biomarkers early phase clinical trial good laboratory practice immunogenicity individual patient innovation interstitial meetings mouse model nanoGold nanomedicine novel phase 1 study phase 2 study prevent prototype renal damage screening success urinary young woman

项目摘要

Abstract Systemic lupus erythematosus (SLE) or lupus is an autoimmune disease that affects more than 5 million people worldwide, including 1.5 million Americans. Nearly 60% of these patients will develop lupus nephritis, which can cause kidney failure. Thus, its financial burden to individual patient can reach $70,000/year, much higher than many other diseases because of kidney transplantation. Although early treatment of lupus nephritis can significantly slow down or even prevent the disease progression to kidney failure, proteinuria, our current clinical standard for screening lupus patients, is not sensitive and accurate enough for early detection of lupus nephritis. While new endogenous biomarkers or exogenous markers are being tested in clinical trials for early diagnosis of lupus nephritis, none of them has outperformed proteinuria in the clinics. As a result, even today, proteinuria remains the clinical standard and there are strong unmet needs for early detection and accurate monitoring of kidney damages in the lupus patients. To address this unmet need, ClearNano Inc. is developing a test agent, named “ClearGold” that can be used as an exogenous urine marker to detect lupus nephritis much earlier and more accurately than proteinuria. Sponsored by previous STTR Phase I grant, using a renal clearable gold nanoparticle as a prototype test agent, ClearNano has successfully validated the feasibility of ClearGold in detection and staging of lupus nephritis in mouse model much earlier and more accurately than proteinuria, and found it also outperformed other classical endogenous and exogenous markers being evaluated in the clinical trials for lupus nephritis detection. In this STTR Phase II application, we will identify a lead product, develop large-scale synthesis under Good Laboratory Practice (GLP) guidelines and conduct in-house toxicity study in rat model. The success will allow us to prepare a strong package for pre-Investigational New Drug (IND) meeting with FDA, reduce the risk for comprehensive toxicology studies carried by CRO, and accelerate the clinical translation of this novel nanotechnology; so that a long-standing unmet need in the early detection of lupus nephritis can be eventually addressed with our “ClearGold” test agent, which represents a $1.6 Billion market opportunity.

抽象的系统性红斑狼疮 (SLE) 或狼疮是一种自身免疫性疾病，影响超过 500 万人全世界的人，包括 150 万美国人，其中近 60% 会患上狼疮肾炎，因此，其对个别患者的经济负担可达每年 70,000 美元。因为肾移植虽然早期治疗狼疮性肾炎高于许多其他疾病。可以显着减缓甚至预防疾病进展为肾衰竭、蛋白尿，我们目前筛查狼疮患者的临床标准对于狼疮的早期检测不够灵敏和准确虽然新的内源性生物标志物或外源性标志物正在临床试验中进行早期测试。狼疮性肾炎的诊断，在临床上没有一个比蛋白尿表现更好，因此，即使在今天，蛋白尿仍然是临床标准，早期检测和准确诊断的需求尚未得到满足。为了满足这一未满足的需求，ClearNano Inc. 正在开发监测狼疮患者肾脏损伤的技术。一种名为“ClearGold”的测试剂，可作为外源性尿液标记物来检测狼疮性肾炎比蛋白尿更早、更准确，由之前的 STTR 一期资助资助，使用肾脏可清除的方法。金纳米粒子作为原型测试剂，ClearNano 已成功验证了 ClearGold 在在小鼠模型中进行狼疮性肾炎的检测和分期比蛋白尿更早、更准确，并且发现它也优于临床中评估的其他经典内源性和外源性标记物狼疮性肾炎检测试验在 STTR II 期应用中，我们将确定主导产品并开发。根据良好实验室规范 (GLP) 指南进行大规模合成，并进行内部毒性研究大鼠模型的成功将使我们能够为研究前新药（IND）准备一个强有力的方案。与FDA会面，降低CRO进行综合毒理学研究的风险，加速这种新型纳米技术的临床转化，以满足早期检测方面长期未满足的需求；狼疮性肾炎最终可以通过我们的“ClearGold”测试剂得到解决，这相当于 16 亿美元市场机会。