Flow Responsive Embolic Agent for the Complete Devascularization of Meningiomas

用于脑膜瘤完全断流的血流响应栓塞剂

基本信息

批准号：
10405029
负责人：
QUYNH P PHAM
金额：
$ 111.74万
依托单位：
ARSENAL MEDICAL, INC.
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-05-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10405029
关键词：
Acute Adoption Animals Area Benign Biocompatible Materials Biological Biological Assay Blood flow Brain Brain Neoplasms Chemicals Clinic Clinical Collaborations Communities Complement Cyanoacrylates Data Data Set Development Device Designs Distal Effectiveness Ethylene Oxide Evaluation Evolution Excision Exhibits External Carotid Artery Branch Family suidae Feasibility Studies Formulation Foundations Glues Goals Grant Hemorrhage Human Implant In Situ Injections Kidney Label Lead Learning Life Liquid substance Manuals Mediation Medical Methods Neurosurgeon New Agents Operative Surgical Procedures Pain Paste substance Pathway interactions Patient Care Patients Penetration Performance Phase Physicians Polyvinyl Alcohol Precipitation Prevention Procedures Property Radiology Specialty Reflux Reporting Research Risk Safety Silicones Small Business Innovation Research Grant Solvents Sterilization Structure Syringes System Technology Testing Therapeutic Embolization Thinness Time Toxicology Trauma United States Universities Vascular blood supply Viscosity Work animal data base biomaterial compatibility brain tumor resection cohort commercialization cost effective cytotoxicity design experience first-in-human hemocompatibility human data human study in vivo innovation meningioma neurosurgery neurovascular novel off-label use particle pre-clinical research preclinical study prevent professor programs research clinical testing response risk mitigation secondary endpoint standard of care success systemic toxicity tumor usability

项目摘要

PROJECT SUMMARY Significance: Pre-operative embolization (POE) of meningiomas is an established neuroendovascular procedure performed to reduce the extensive amount of blood loss that occurs during tumor resection. The current practice is significantly hampered because of efficacy and safety deficiencies of current embolic agents used off-label for this indication (none of which are designed specifically for POE). Polyvinyl alcohol particles are the most used embolic agent, but efficacy data raise concerns of their clinical benefit. Trufill and Onyx are liquid-based embolic alternatives but are fraught with limitations of their own. For example, Onyx contains toxic solvent that causes patient pain and discomfort while the technical risks associated with Trufill have negated its wide-spread adoption in the United States. Thus, there is a need for an easy-to-use, on-label embolic agent designed specifically for POE of meningiomas that provides safe and complete devascularization. Such an embolic would result in faster and safer surgical resection, representing a significant evolution in the treatment of meningioma patients. Approach: In this Direct to Phase II SBIR, Arsenal Medical will advance its shear-thinning biomaterial technology, a flow responsive embolic (FRE) agent, as a therapy for the POE of meningiomas. For POE to be effective, complete devascularization of the meningioma is desired, which is achieved by total occlusion of all distal vessels that supply the tumor. Our Phase I results have demonstrated that the FRE exhibits superior distal penetration compared to commercial liquid embolics, is biocompatible, and can be manually injected through a neurovascular microcatheter. The goal of this proposal is to advance the proof-of-concept formulation towards a product configuration that is ready for clinical testing via an early feasibility study (EFS), enabling an efficient path to commercialization. In Aim 1, we will finalize the delivery system and affirm the product’s usability with clinicians. Aim 2 will consist of selection of a commercially viable sterilization method, followed by confirmation of product shelf-life. Biocompatibility of the FRE will be confirmed via a pre-clinical study to determine the neurovascular response and safety (Aim 3) and ISO10993 biocompatibility testing through biological and chemical characterization assays (Aim 4). The proposed work provides a foundational data set that will be complemented with post-Phase II activities to advance towards commercialization. Innovation: The FRE biomaterial has adaptive properties enabling it to become a low viscosity fluid under high shear that penetrates and fills the distal vessels supplying the meningioma. As embolization progresses, flow and shear will continually decrease; in response, the FRE progressively increases in viscosity becoming a viscous paste for controlled injection. The result is complete casting and occlusion of the entire vasculature. Compared to other liquid embolics, the FRE is less susceptible to incomplete occlusion because its solidification mechanism occurs independent of its microenvironment. Onyx, for example, solidifies via a precipitation effect, forming a hard outer shell that can block vessel branch pathways preventing them from deep vessel embolization.

项目概要意义：脑膜瘤术前栓塞（POE）是一种既定的神经血管内手术进行该手术是为了减少肿瘤切除过程中发生的大量失血。由于目前标签外使用的栓塞剂的功效和安全性缺陷，该治疗受到严重阻碍。此指示（都不是专门为 POE 设计的）聚乙烯醇颗粒是使用最多的。 Trufill 和 Onyx 是基于液体的栓塞剂，但疗效数据引起了人们对其临床益处的担忧。替代品，但其自身也充满局限性，例如，Onyx 含有有毒溶剂，会导致。患者疼痛和不适，而 Trufill 相关的技术风险阻碍了其广泛采用因此，在美国需要一种专门为 POE 设计的易于使用、标签上的栓塞剂。提供安全和完全断流的脑膜瘤将导致更快和更快速的栓塞。更安全的手术切除代表了脑膜瘤患者治疗的重大进展。方法：在直接进入第二阶段 SBIR 中，Arsenal Medical 将推进其剪切稀化生物材料技术，血流反应性栓塞 (FRE) 剂，作为脑膜瘤 POE 的治疗方法，使 POE 有效、彻底。需要对脑膜瘤进行断流术，这是通过完全闭塞所有远端血管来实现的我们的 I 期结果表明，与 FRE 相比，FRE 具有更优异的远端穿透能力。商业液体栓塞，具有生物相容性，可以通过神经血管手动注射该提案的目标是推进产品的概念验证配方。配置已准备好通过早期可行性研究 (EFS) 进行临床测试，从而提供一条有效的途径在目标1中，我们将最终确定交付系统并确认产品的可用性。目标 2 将包括选择商业上可行的灭菌方法，然后确认产品 FRE 的生物相容性将通过临床前研究来确定，以确定神经血管。通过生物和化学进行反应和安全性（目标 3）和 ISO10993 生物相容性测试表征分析（目标 4）。拟议的工作提供了一个将得到补充的基础数据集。与第二阶段后的活动一起推进商业化。创新：FRE生物材料具有适应性特性，使其能够在高温下成为低粘度流体随着栓塞的进展，剪切力会穿透并填充供应脑膜瘤的远端血管。剪切力将不断减小；作为响应，FRE 的粘度逐渐增加，成为粘稠糊状物与其他注射相比，其结果是整个脉管系统的完全铸造和闭塞。液体栓塞，FRE 不太容易受到不完全闭塞的影响，因为它会发生凝固机制例如，缟玛瑙通过沉淀效应凝固，形成坚硬的外层。外壳可以阻塞血管分支通路，防止深部血管栓塞。