PERCUTANEOUS TREATMENT OF PERIPHERAL ARTERIAL OCCLUSIVE DISEASE WITH IMPLANTATION OF MULTIPLE, BALLOON-EXPANDABLE, DRUG-ELUTING BIORESORBABLE SCAFFOLDS (the Efemoral Vascular Scaffold System)

心血管疾病是人类健康和长寿的巨大负担；到2030年，超过400 将有100万人患上这种疾病，其中每年的死亡率超过2300万。血管疾病 影响下肢动脉的疾病被称为“外周动脉闭塞症”(PAOD)，是一种流行病 影响到大约10%的50岁以上人口和20%的70岁以上人口。 它的流行正在以惊人的速度增长，在过去的十年里增长了20%以上。症状性多器官功能障碍 导致行动不便、身体健康不良、生活质量下降、过早衰退和过早死亡。 PAOD的身体负担比充血性心力衰竭更大，长期预后是 比得了冠状动脉疾病还糟糕。据估计，11%的患有PAOD的患者中 这种疾病的严重形式：严重的肢体缺血(CLI)。CLI发生在PAOD的闭塞病变具有 变得如此众多和严重，以至于四肢的基线灌流不足以维持其 生存能力。它的预后令人沮丧；只有大约一半的受影响患者将活着，只有6条肢体可以存活 在确诊后的几个月内。 对有症状的PAOD患者的标准护理是经皮外周介入(PPI) 包括球囊血管成形术、药物包衣球囊血管成形术、经皮动脉粥样硬化术、 以及裸露和药物洗脱的自膨式支架。不幸的是，可用的有效性和耐用性 设备有限，因为高达50%的传统血管内操作会因动脉并发症而变得复杂 1年内再狭窄和复发。这项研究方案描述了小说的发展， 系列、球囊可膨胀、可吸收、药物洗脱支架，旨在提供更即时有效的 和持久的血管内治疗症状性股静脉窝闭塞症。 与大多数外周血管内装置不同的是，这些装置只是冠状动脉的改编和“放大” 股外血管支架系统(EVSS)是专门为 外周血管系统。它的设计利用了已知的血管生物学原理，包括：(1)刚性 通过球囊扩张展开的设备代表了血管内支架的最佳设计，因为它 对动脉壁的瞬时影响和相对容易的精确植入，(2)长而硬的装置不能 安全地植入随着骨骼运动而弯曲和扭曲的动脉，(3)弯曲和扭曲的长动脉 可以通过多个短支架有效地治疗，这些支架允许介入的非支架动脉节段 为了不受阻碍地移动，(4)支架段的长度、数目和间距可由 已知的目标动脉的弯曲特征，以及(5)动脉只需要临时支架； 支架的溶解将促进动脉的长期愈合，并避免留置的晚期并发症。 异物。 电子股份公司成立于2015年，其使命是开发一种新型的、可膨胀的、可吸收的药物洗脱支架，旨在提供更简单、有效和耐用的支架 症状性股腓窝闭塞症的血管内治疗。股外血管支架的构建 系统(EVSS)是一种廉价且易于制造的生物兼容设备，它是在 与简单的血管成形术气球的方式相同。来自介入血管外科医生的私人资金 放射科医生、介入性心脏病专家、独立投资者、朋友和家人建立了电子股份公司 医疗公司作为一家持续经营的公司，通过其设计、原型、生化、 机械、毒理学和临床前概念验证阶段。人类历史上第一次，早期的可行性， 国际临床试验招募了6名患者，效果良好。 这项直接第二阶段SBIR建议的目的是证明 股外血管支架系统(EVSS)为启动临床早期可行性研究做准备 (EFS)在美国。它的具体目标是：(1)证明设备的长期安全性和有效性 经皮外周血管介入的GLP临床前模型，(2)定量设备洗脱，附图 GLP经皮给药临床前模型的药物转移、全身暴露和药代动力学 外周血管介入，以及(3)临床前GLP支架溶解动力学的量化 经皮外周血管介入治疗模型。

Cardiovascular disease is a tremendous burden on human health and longevity; by the year 2030, over 400 million people will have the disease including an annual mortality of more than 23 million. Vascular disease affecting the lower extremity arteries, known as “peripheral arterial occlusive disease” (PAOD), is an epidemic affecting approximately 10% of the population over the age of 50 and 20% of the population over the age of 70. Its prevalence is increasing at an alarming rate, by more than 20% over the last decade. Symptomatic PAOD causes loss of mobility, poor physical health, decreased quality of life, premature decline and early mortality. The physical burden of PAOD is greater than having congestive heart failure and the long-term prognosis is worse than having coronary artery disease. An estimated 11% of patients afflicted with PAOD have the most severe form of the disease: critical limb ischemia (CLI). CLI occurs when the occlusive lesions of PAOD have become so numerous and severe that the baseline perfusion of the extremity is inadequate to sustain its viability. It carries a dismal prognosis; only about half of affected patients will be alive with viable limbs only six months after the diagnosis is made. The standard-of-care for patients with symptomatic PAOD is percutaneous peripheral intervention (PPI) including the techniques of balloon angioplasty, drug-coated balloon angioplasty, percutaneous atherectomy, and bare and drug-eluting self-expanding stenting. Unfortunately, the effectiveness and durability of available devices is limited as up to 50% of conventional endovascular procedures will be complicated by arterial restenosis and recurrence within the first year. This research proposal describes the development of novel, serial, balloon-expandable, resorbable, drug-eluting scaffold designed to provide more immediately effective and durable endovascular treatment of symptomatic femoropopliteal occlusive disease. Unlike most peripheral intravascular devices that are simply adaptations and “scale-ups” of coronary devices, the Efemoral Vascular Scaffold System (EVSS) is specifically designed for the unique environment of the peripheral vasculature. Its design exploits known principles of vascular biology including that, (1) a rigid device that is deployed via balloon expansion represents the optimal design of an intravascular stent given its transient effect on the arterial wall and relative ease of precise implantation, (2) a long, rigid device cannot be safely implanted in an artery that bends and twists with skeletal motion, (3) long arteries that bend and twist could be effectively treated with multiple, short stents that allow the intervening, non-stented arterial segments to move unencumbered, (4) the length, number and spacing of the stent segments could be determined by the known bending characteristics of the target arteries, and (5) arteries need only be scaffolded transiently; late dissolution of the stent will facilitate long-term arterial healing and avoid the late complications of an indwelling foreign body. Efemoral Medical, Inc., was founded in 2015 with the mission of developing a novel, balloonexpandable, resorbable, drug-eluting scaffold designed to provide more simple, effective and durable endovascular treatment of symptomatic femoropopliteal occlusive disease. The Efemoral Vascular Scaffold System (EVSS) is a cheap and easily-manufactured biocompatible device that is prepared and deployed in an identical manner to simple angioplasty balloons. Private funding from vascular surgeons, interventional radiologists, interventional cardiologists, independent investors, friends and family established Efemoral Medical, Inc. as a going concern and developed the device through its design, prototype, biochemical, mechanical, toxicologic and pre-clinical proof-of-concept phases. A first-in-human, early feasibility, international clinical trial has enrolled six patients with good results. The purpose of this Direct Phase II SBIR proposal is to demonstrate the pre-clinical safety and efficacy of the Efemoral Vascular Scaffold System (EVSS) in preparation for initiation of a clinical Early Feasibility Study (EFS) in the United States. It’s Specific Aims are, (1) To demonstrate long-term device safety and efficacy in a GLP pre-clinical model of percutaneous peripheral vascular intervention, (2) To quantify device elution, mural drug transfer, systemic exposure and pharmacokinetic profile in a GLP pre-clinical model of percutaneous peripheral vascular intervention, and (3) To quantify the kinetics of scaffold dissolution in a GLP pre-clinical model of percutaneous peripheral vascular intervention.