Clinical study to enable commercialization of nonsurgical gel patch for eardrum repair

摘要 慢性鼓膜穿孔(TM)每年影响美国超过17万名患者， 通常源于TM中插入的通气管，以排出中耳感染的液体。听之任之， 这些TM穿孔可导致显著的发病率，包括反复耳部感染、传导性和 感觉神经性听力损失、乳突骨感染和胆脂瘤的发展。目前，TM穿孔 通过侵入性手术将移植物应用于TM修复，可能需要2-4个小时才能完成，成本较高 到每台手术18,000美元，并对儿科患者带来与麻醉相关的重大风险。非手术治疗 可以减少手术时间和发病率的现有程序的替代方案将是经济的 对患者、耳鼻喉科医生和付款人都有好处。 我们已经开发了一种名为Perf-Fix的高度可再生的凝胶贴片，用于非手术TM修复，适合 现有鼓膜成形术的临床工作流程。PERF-Fix可通过耳道应用于TM，而无需 穿孔边缘的伤口或磨损，然后通过蓝光将其固化到坚硬的支架上，细胞通过该支架 可以迁移。细胞在增殖和迁移时降解凝胶贴片，导致完全取代 PERF-修复再生的TM组织。在这项建议中，我们将在成人和儿童中进行人体研究 患者评价Perf-Fix的疗效。这项人体研究是Perf提交前的最后一个里程碑- 向FDA申请批准为II类医疗设备。在研究期间，患者将接受以下评估：穿孔 闭合率、应用时间、闭合时间、听力分数变化、器械不良反应安全性 事件和故障率。本研究的终点包括：3周和3个月的TM闭合率、发生率 不良事件、程序成功和功能性听证结果。这项研究的数据将被汇编 最终报告将包括在提交给FDA的从头报告中。该SBIR项目以 提交从头申请。这一提议的成功将为市场提供必要的数据 PERF-在产品发布后成功修复，导致比目前的 医疗保健成本大幅降低的标准医疗服务。

ABSTRACT Chronic perforations of the tympanic membrane (TM) affect over 170,000 patients in the United States annually, often stemming from ventilation tubes inserted in the TM to drain fluid from middle ear infections. Left untreated, these TM perforations can lead to significant morbidities that include recurrent ear infection, conductive and sensorineural hearing loss, mastoid bone infection, and cholesteatoma development. Currently, TM perforations are repaired with a graft applied to the TM via an invasive surgery that can take 2-4 hours to complete, cost up to $18,000 per surgery, and carry significant anesthesia-related risks for pediatric patients. A nonsurgical alternative to the existing procedure that can reduce procedure time and morbidities would be of economic benefit to patients, otolaryngologists, and payors alike. We have developed a highly regenerative gel patch called Perf-Fix for nonsurgical TM repair that fits the existing clinical workflow for myringoplasty. Perf-Fix can be applied to the TM through the ear canal without incisions or abrasion of the perforation margin, then cured via blue light into a stiff scaffold through which cells can migrate. The cells degrade the gel patch as they proliferate and migrate, resulting in total replacement of Perf-Fix with regenerated TM tissue. In this proposal, we will conduct a human study in both adult and pediatric patients to evaluate the efficacy of Perf-Fix. This human study is the last milestone before submission of Perf- Fix to FDA for clearance as a class II medical device. During the study, patients will be evaluated for: perforation closure rate, application time, time to closure, changes in hearing scores, safety of device through adverse events and failure rates. The endpoints for this study include: TM closure rate at 3 weeks and 3 months, incidence of adverse events, procedural success, and functional hearing results. The data from this study will be compiled in a final report that will be included in the de novo submission to FDA. This SBIR project concludes with submission of the de novo application. The success of this proposal will supply the necessary data to market Perf-Fix successfully after product launch, leading to a significant medical improvement over the current standard-of-care with a major reduction in healthcare costs.