Sustained Release Inner Ear Delivery of Corticosteroid

描述（由申请人提供）：在过去的二十年中，耳蜗植入体已经恢复了数千名患者的听力。然而，由于残余听力在插入过程中受损，因此这种有价值的手术仅限于深度或完全耳聋的患者。许多严重听力损失的患者，一个更大的群体，目前没有植入，因为担心失去他们的残余听力。类固醇已被证明对耳蜗创伤引起的听力损失有保护作用。O-Ray的药物输送技术直接从耳蜗植入电极释放类固醇，减少手术相关的炎症，从而防止残余听力损失。O-Ray人工耳蜗的成功开发将对每年数十万患者产生巨大影响，这些患者现在可以使用该设备恢复听力。O-Ray的团队已经在动物模型中证明了其类固醇释放人工耳蜗植入物的安全性和有效性，并生产了一个原型设备。该IIB期提案基于FDA的反馈，涉及完成启动临床试验的监管批准所需的所有步骤。该提案的具体目标有三个方面：首先，O-Ray人工耳蜗电极的良好生产规范（GMP）生产用于临床试验的类固醇。第二，所制造的类固醇洗脱电极的表征。这将包括体外试验，以测定电极的物理和化学性质，以及成品器械中药物的稳定性。最后，将进行含缓释类固醇的人工耳蜗电极的安全性研究，以验证该器械用于人体的安全性。O-Ray的研究人员团队是唯一有资格执行本文提出的工作的团队，并且在耳科、药物开发和药物输送方面具有成功开发本产品的专业知识。O-Ray的科学家们已经成功地开发出了目前正在临床上使用的治疗配方。这包括眼内持续释放类固醇植入物，其能够从单次植入起维持抗炎性玻璃体内药物水平长达三年。在这项工作完成后，将向FDA提交IDE，以批准开始临床试验。在这一点上，O-Ray将出售其产品给一家大型人工耳蜗植入公司，以开始临床试验并将产品推向市场。

DESCRIPTION (provided by applicant): Cochlear implants have restored hearing in thousands of patients over the last two decades. However, because residual hearing is damaged in the process of insertion, this valuable procedure has been restricted to those patients with profound or total deafness. Many patients with severe hearing loss, a far larger group, are not currently implanted for fear of losing their residual hearing. Steroids have been shown to have a protective effect against hearing loss caused by cochlear trauma. O-Ray's drug delivery technology releases steroids directly from a cochlear implant electrode, decreasing surgery associated inflammation and, in turn, protecting against residual hearing loss. The successful development of O-Ray's cochlear implant for the preservation of residual hearing would have a dramatic impact on hundreds of thousands of patients each year that would now be able to restore hearing using this device. O-Ray's team has demonstrated the safety and efficacy of its steroid releasing cochlear implants in animal models and has produced a prototype device. This Phase IIB proposal is founded on feedback from the FDA and involves the completion of all steps necessary for regulatory approval for the initiation of clinical trials The Specific Aims of this proposal are threefold: First, the Good Manufacturing Practice (GMP) manufacture of O- Ray's cochlear implant electrode with steroid for clinical trials. Second, the characterization of the manufactured steroid eluting electrodes. This will include in vitro tests t assay the physical and chemical properties of the electrode, as well as the stability of the drug in the completed device. Lastly, safety studies of cochlear implant electrode with extended release steroid will be performed to verify the safety of the device for human use. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, drug development and drug delivery for the successful development this product. O-Ray scientists have successfully developed therapeutic formulations that are currently being used in the clinic. This includes an intraocular sustained release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for periods of up to three years from a single implantation. At the completion of this work, an IDE will be filed with the FDA for the approval to commence clinical trials. At this point, O-Ray will sell its product to a large cochlear implant company for commencement of clinical trials and introduction of the product to the marketplace.