Nitric oxide releasing bionanomatrix to enhance dialysis fistula maturation

一氧化氮释放生物纳米基质促进透析瘘成熟

基本信息

批准号：
10257495
负责人：
Patrick Hwang
金额：
$ 94.08万
依托单位：
ENDOMIMETICS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2023-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10257495
关键词：
Address Adverse effects Americas Animal Model Animals Arteriovenous fistula Blood Vessels Blood flow Cell Proliferation Clinical Clinical Trials Consult Contracts Development Dialysis procedure End stage renal failure Endothelium Enzymes Evaluation Exhibits FDA approved Family suidae Fistula Formulation Functional disorder Funding Future Gel Goals Grant Guidelines Health Expenditures Hemodialysis Human Hyperplasia In Vitro Inflammation Inflammatory Response International Legal patent Licensing Mediating Modeling Morbidity - disease rate Nitric Oxide Patients Peptide Synthesis Peptides Pharmacologic Substance Phase Phase I Clinical Trials Plants Positioning Attribute Preparation Process Property Protocols documentation Public Health Rattus Renal Replacement Therapy Research Risk Rodent Site Small Business Innovation Research Grant Smooth Muscle Myocytes Sterilization Strategic Planning Technology Testing Text Thrombosis Time United States Vascular remodeling Vasodilation Venous base biomaterial compatibility clinical application commercialization cost effective therapy good laboratory practice improved in vivo industry partner infection rate infection risk mortality novel phase 2 study research and development standardize guidelines viscoelasticity

项目摘要

Over 725,000 patients have end stage renal disease, with nearly 90% utilizing hemodialysis for renal replacement therapy. A functioning and durable vascular access is required, and an arteriovenous fistula (AVF) is preferred due to a lower rate of infections, thrombosis, and healthcare expenditures. However, after formation, approximately 60% of AVFs fail to mature, due to early intimal hyperplasia and inadequate vasodilation. At present, there are no effective therapies to promote vascular access maturation. The annual cost of treating vascular access dysfunction totals over $1 billion US dollars. Endomimetics has developed a nitric oxide (NO) releasing bionanomatrix gel (“AVF Gel”) that improves the maturation of AVFs by inhibiting intimal hyperplasia, enhancing vasodilation, and reducing inflammation. Through SBIR Phase I and II grant funding, this AVF Gel has been evaluated in both small and large animal models (rat and pig), demonstrating improved blood flow and inhibition of intimal hyperplasia. In this Phase IIB proposal, we propose Aims that will prepare Endomimetics to meet FDA requirements for Phase I clinical trials. These Aims include 1) Development of a manufacturing plan with AmbioPharm for large scale peptide synthesis and with Bioserv America for formulation, fill and finish, sterilization, and packaging that is consistent with FDA requirements and 2) Perform stability and biocompatibility evaluations of the AVF Gel in vitro and in vivo based on The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) and International Organization for Standardization (ISO) guidelines. We are beginning the FDA review process, and an initial conversation with the FDA occurred on March 4, 2020, in which the FDA was consulted on future steps necessary to advance to Phase I clinical trials. Commercialization of the Endomimetics AVF Gel may provide significant improvement in the treatment of patients requiring dialysis.

超过725,000名患者患有终阶段肾脏疾病，使用血液透析进行肾脏替代疗法，近90％。需要功能耐用且耐用的血管通道，并且由于感染率较低，血栓形成和医疗保健支出，因此首选动静脉瘘（AVF）。然而，在形成后，由于早期内膜增生和血管舒张不足，大约60％的AVF无法成熟。目前，尚无有效的疗法来促进血管通道成熟。治疗血管通道功能障碍的年度成本超过10亿美元。内属材料已经开发了一种一氧化氮（NO）释放bionanomatrix凝胶（“ AVF凝胶”），该氧化物通过抑制内膜增生，增强血管舒张和减少炎症来改善AVF的成熟。通过SBIR I阶段和II授予的资金，该AVF凝胶已在小型和大型动物模型（大鼠和猪）中进行了评估，证明了血液流动的改善和内膜增生的抑制作用。在此阶段的IIB提案中，我们提出的目标是准备内含物，以满足I期临床试验的FDA要求。这些目的包括1）制定具有大规模肽合成的制造计划，以及与BioServ America一起制定与FDA要求一致的配方，填充和填充，灭菌和包装，2）基于国际化的稳定性和生物相容性评估，以实现AVF凝胶的稳定性，以实现国际委员会的统一化（用于国际委员会），以实现人类的统一化（人为统一），以辅助（人类）的统一性（carumantization in International conconiation for Huthroutical contranization for Huthroutical intherical intarmace for Sartionical concolyation for Huthroutical conconiation（（ISO）指南。我们正在开始FDA审查过程，并于2020年3月4日与FDA进行初步对话，其中向FDA咨询了FDA，以促进I期临床试验所需的未来步骤。内属纤维凝胶的商业化可能会在需要透析的患者治疗中得到显着改善。