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

通过植入多个可扩张球囊、药物洗脱生物可吸收支架（股动脉血管支架系统）经皮治疗外周动脉闭塞性疾病

• 批准号: 10545226
• 负责人: Lewis Schwartz
• 金额: $ 78.31万
• 依托单位: EFEMORAL MEDICAL, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-19 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10545226
• 关键词: Acute; Affect; Age; Aging; American; Amputation; Arterial Occlusive Diseases; Arteries; Atherectomy; Balloon Angioplasty; Balloon Dilatation; Biochemical; Biology; Blood Circulation; Blood Vessels; Blood flow; Bypass; Cardiovascular Diseases; Characteristics; Chronic; Chronic Disease; Clinical; Clinical Research; Clinical Trials; Confusion; Congestive Heart Failure; Coronary; Coronary Arteriosclerosis; Development; Device Safety; Devices; Diagnosis; Dilatation - action; Disease; Drug Kinetics; Effectiveness; Enrollment; Environment; Epidemic; Excess Mortality; Failure; Family; Feasibility Studies; Foreign Bodies; Friends; Funding; Goals; Health; Human; Implant; International; Intervention; Ischemia; Kinetics; Lead; Left; Leg; Legal patent; Length; Lesion; Limb structure; Longevity; Lower Extremity; Mechanics; Medical; Metals; Mission; Modality; Morbidity - disease rate; Morphology; Motion; Operative Surgical Procedures; Outcome; Paclitaxel; Patient Care; Patients; Perfusion; Peripheral; Peripheral Vascular Diseases; Persons; Pharmaceutical Preparations; Phase; Plague; Population; Pre-Clinical Model; Preclinical Testing; Preparation; Prevalence; Privatization; Procedures; Process; Prognosis; Quality of life; Recurrence; Research Proposals; Safety; Small Business Innovation Research Grant; Stenosis; Stents; Surgeon; Surgical incisions; Survivors; Symptoms; System; Techniques; Technology; Therapeutic; Toxicology; United States; United States Food and Drug Administration; Vascular Diseases; antiproliferative drugs; biomaterial compatibility; clinical practice; cost; critical limb Ischemia; design; disability; experimental study; first-in-human; functional decline; healing; hospital readmission; implantation; limb loss; medical specialties; mortality; nitinol; novel; novel therapeutics; physical conditioning; pre-clinical; preclinical safety; preclinical study; premature; preservation; prototype; radiologist; restenosis; restoration; scaffold; skeletal; standard of care; symptom treatment; treatment choice; virtual

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.

心血管疾病是人类健康和寿命的巨大负担;到2030年，超过400 2000万人将患上这种疾病，包括每年超过2300万人的死亡率。血管疾病 影响下肢动脉的一种称为“外周动脉闭塞性疾病”（PAOD）的流行病 影响约10%的50岁以上人口和20%的70岁以上人口。 其流行率正以惊人的速度增长，在过去十年中增长了20%以上。症状PAOD 导致丧失行动能力、身体健康状况不佳、生活质量下降、过早衰退和过早死亡。 PAOD的身体负担大于充血性心力衰竭，长期预后为 比冠心病还严重据估计，11%的PAOD患者有最多的 严重形式的疾病：严重肢体缺血（CLI）。当PAOD的闭塞性病变 变得如此之多和严重，肢体的基线灌注不足以维持其 生存能力它的预后很差;只有大约一半的受影响患者能够存活，只有六个肢体可以存活。 在诊断后的几个月内。 症状性PAOD患者的标准治疗是经皮外周介入治疗（PPI） 包括球囊血管成形术、药物涂层球囊血管成形术、经皮动脉粥样硬化切除术 以及裸支架和药物洗脱自扩张支架。不幸的是，现有的有效性和耐用性 由于高达50%的传统血管内手术将因动脉栓塞而复杂化， 再狭窄和第一年内复发。本研究计划描述了新的， 一系列的、球囊扩张的、可吸收的、药物洗脱支架，旨在提供更立即有效的 和持久的血管内治疗症状性股腘动脉闭塞性疾病。 与大多数外周血管内设备不同，这些设备只是冠状动脉的适应和“放大”， Efemoral血管支架系统（EVSS）是专门为以下独特环境设计的： 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器械代表了血管内支架的最佳设计， 对动脉壁的短暂影响和精确植入的相对容易，（2）长的刚性装置不能 安全植入随骨骼运动弯曲和扭曲的动脉中，（3）弯曲和扭曲的长动脉 可以用多个短支架有效治疗， 为了不受阻碍地移动，（4）支架段的长度、数量和间距可以由 目标动脉的已知弯曲特性，以及（5）动脉仅需要瞬时地搭建;晚期 支架的溶解将促进长期动脉愈合并避免留置的晚期并发症 异物 Efemal Medical，Inc.，成立于2015年，其使命是开发一种新颖的气球，可膨胀的、可再吸收的、药物洗脱支架，设计用于提供更简单、有效和耐用的 症状性股腘动脉闭塞性疾病的血管内治疗。股动脉血管支架 系统（EVSS）是一种廉价且易于制造的生物相容性设备，可在 与简单的血管成形术球囊相同的方式。来自血管外科医生的私人资金，介入 放射科医生，介入心脏病专家，独立投资者，朋友和家人建立了Efemal 医疗用品有限公司作为一个持续的企业，并通过其设计，原型，生化， 机械、毒理学和临床前概念验证阶段。一个首次在人体上的早期可行性， 国际临床试验已招募了6名患者，效果良好。 本直接II期SBIR提案的目的是证明以下药物的临床前安全性和疗效： 股动脉血管支架系统（EVSS），准备启动临床早期可行性研究 (EFS)在美国其具体目的是：（1）证明器械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）为了量化器械洗脱，壁 GLP临床前经皮给药模型中的药物转移、全身暴露和药代动力学特征 外周血管干预，和（3）量化GLP临床前研究中支架溶解的动力学 经皮外周血管介入模型。