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

• 批准号: 10258130
• 负责人: Mengxiao Yu
• 金额: $ 80.99万
• 依托单位: CLEARNANO, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-19 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10258130
• 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' 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

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 全身性红斑狼疮（SLE）或狼疮是一种自身免疫性疾病，影响超过500万 全球人，包括150万美国人。这些患者中有将近60％会出现狼疮肾炎， 这会导致肾衰竭。那就是，它对个体患者的财务燃烧可以达到70,000美元，很多 由于肾脏移植，高于许多其他疾病。尽管早期治疗狼疮肾炎 可以显着减慢，甚至可以防止疾病发展为肾衰竭，蛋白尿，我们的当前 筛查狼疮患者的临床标准不足以敏感和准确，无法早日检测 肾炎。虽然在临床试验中测试了新的内源性生物标志物或外源标记的早期 狼疮性肾炎的诊断，在诊所中，没有一个都表现出色。结果，即使在今天 蛋白尿症仍然是临床标准，并且有很强的未满足的需求，需要早期检测和准确 监测狼疮患者的肾脏损伤。为了满足这种未满足的需求，Clearnano Inc.正在开发 一种被称为“ Cleargold”的测试剂，可以用作外源尿液标记物来检测狼疮肾炎 比蛋白尿早，更准确。由以前的STTR I期赠款赞助，使用肾脏清除 金纳米颗粒作为原型测试剂，Clearnano成功验证了Cleasgold的可行性 小鼠模型中狼疮肾炎的检测和分期比蛋白尿更早，更准确，并且 发现它也优于在临床上评估的其他经典内源性和外源标记 狼疮肾炎检测试验。在此STTR II阶段应用中，我们将确定铅产品，开发 根据良好实验室实践（GLP）指南和内部毒性研究，大规模合成 大鼠模型。成功将使我们能够为预先注射的新药（IND）准备一个强大的包装 与FDA会面，降低CRO进行全面毒理学研究的风险，并加速 这种新型纳米技术的临床翻译；因此，早期发现长期未满足的需求 狼疮肾炎最终可以用我们的“ Cleargold”测试剂来解决，该测试剂代表16亿美元 市场机会。