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

摘要 鼓膜（TM）的慢性穿孔每年影响美国超过170，000名患者， 通常源于插入TM中的通气管，以排出中耳感染的液体。如果不治疗， 这些TM穿孔可导致显著的发病率，包括复发性耳部感染、传导性和 感音神经性听力损失、乳突骨感染和中耳乳突瘤发展。目前，TM穿孔 通过侵入性手术将移植物应用于TM进行修复，可能需要2-4小时才能完成， 每例手术的费用高达18，000美元，并对儿科患者带来重大的麻醉相关风险。非手术 替代现有程序，可以减少程序时间和发病率将是经济的 对患者、耳鼻喉科医生和付款人都有好处。 我们开发了一种高度再生的凝胶贴片，称为Perf-Fix，用于非手术TM修复， 鼓膜成形术的现有临床工作流程。Perf-Fix可通过耳道应用于TM， 切口或磨损穿孔边缘，然后通过蓝光固化成坚硬的支架， 可以迁移。细胞在增殖和迁移时降解凝胶贴片，导致完全替换凝胶贴片。 使用再生TM组织进行Perf-Fix。在本提案中，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。这项人体研究是提交Perf之前的最后一个里程碑， 作为II类医疗器械向FDA申请批准。研究期间，将对患者进行以下评价：穿孔 闭合率、应用时间、闭合时间、听力评分变化、器械通过不良事件的安全性 事件和故障率。本研究的终点包括：3周和3个月时的TM闭合率， 不良事件、手术成功率和功能性听力结果。本研究的数据将被汇编 在最终报告中，该报告将包含在向FDA提交的重新分类申请中。该SBIR项目的结论是 重新申请的提交。该提案的成功将为市场提供必要的数据 Perf-Fix在产品发布后成功上市，与目前相比， 标准治疗，大幅降低医疗成本。

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.