IND-enabling Preclinical Development of Sustained Release Inner Ear Delivery of Corticosteroid

皮质类固醇持续释放内耳递送的 IND 临床前开发

• 批准号: 10383347
• 负责人: Matthew Ku
• 金额: $ 88.66万
• 依托单位: O-RAY PHARMA, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-22 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10383347
• 关键词: Address; Adrenal Cortex Hormones; Affect; Animal Model; Animals; Anti-Inflammatory Agents; Autoimmune Inner Ear disease; Businesses; Cavia; Chemistry; Ciprofloxacin; Clinical; Clinical Protocols; Clinical Research; Clinical Trials; Cochlea; Cochlear Implants; Cochlear implant procedure; Complication; Development; Development Plans; Dexamethasone; Disease; Dizziness; Documentation; Dose; Drug Delivery Systems; Drug Kinetics; Ear; Ear Diseases; Environment; FDA approved; Feedback; Fluticasone propionate; Formulation; Frequencies; Goals; Grant; Hearing Protection; Human; Hydrogels; Immune system; Implant; Injections; Investigational Drugs; Investigational New Drug Application; Kinetics; Label; Labyrinth; Lead; Legal patent; Letters; Lifting; Medical; Methods; Names; New Drug Approvals; Operative Surgical Procedures; Oral; Otitis Media; Otology; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Polymer Chemistry; Preparation; Procedures; Protocols documentation; Published Comment; Regulatory Affairs; Research Personnel; Residual state; Safety; Scientist; Site; Steroids; Suggestion; Sustainable Development; Symptoms; Techniques; Technology; Testing; Therapeutic; Therapeutic Index; Tinnitus; Toxic effect; Toxicology; Universities; Virginia; Work; biocompatible polymer; clinical material; common treatment; deaf; design; experience; first-in-human; fluticasone; good laboratory practice; hearing impairment; hearing loss treatment; immune function; implantation; innovation; meetings; novel; novel therapeutics; patient population; phase 1 study; phase 2 study; phase 3 study; pre-clinical; preclinical development; progressive hearing loss; response; safety testing; side effect; stability testing

PROJECT SUMMARY Autoimmune inner ear disease (AIED) is the name given to describe a disorder where the ear is the target of an overactive immune system, causing symptoms of progressive hearing loss and/or dizziness. Most cases of AIED are accompanied by hearing loss and tinnitus that occur over a course of a few months1,2 that progresses rapidly to the second ear, indicative of AIED.3 There are currently no FDA-approved medications for the treatment of AIED, or any type of inner ear hearing loss. The use of high dose oral or intratympanic injection corticosteroids to suppress immune function is the most common treatment for AIED. However, the use of high doses of corticosteroids leads to significant side effects. In response to this unmet medical need, O-Ray Pharma has developed a lead formulation of sustained-release fluticasone pellets (OR-102) for the treatment of AIED that will provide a consistent low dose of corticosteroid to the cochlea over a period of three months. The pellet is implanted directly into the cochlea and releases steroid at the affected site to protect against hearing loss. The OR-102 formulation has demonstrated its safety, pharmacokinetics (PK), and efficacy in multiple guinea pig studies. To test the safety and preliminary efficacy of OR-102 in a first-in-human clinical trial in AIED-affected patients, O-Ray Pharma has submitted an IND application to the FDA. The FDA provided tacit approval of the majority of the application save for a request to perform an additional animal study and suggestions for additional Chemistry/Manufacturing/Control (CMC) work. In response, there were no clinical holds pertaining to the clinical protocol and the chemistry/manufacturing/controls procedures. Thus, the IND is on clinical hold pending the completion of a Good Laboratory Practices (GLP) compliant toxicity and pharmacokinetics study. This IND correspondence has provided us with a clear framework towards an IND allowance. The Specific Aims of this Direct to Phase II proposal are, therefore, to complete the following IND-enabling activities: 1) Drug product manufacturing in accordance with current Good Manufacturing Practices (cGMP) for animal and human trials; 2) Performance of a GLP-compliant guinea pig study as guided by FDA feedback, 3) Preparation and submission of an IND response. The milestone for the successful completion of this grant will be the granting of an IND approval. The team of investigators at O-Ray is uniquely qualified to perform the work proposed herein, and has expertise in otology, regulatory affairs, and business development. O-Ray’s scientists have successfully developed other therapeutic formulations from concept to FDA approval, including an intraocular sustained- release steroid implant capable of maintaining anti-inflammatory intravitreal drug levels for up to three years from a single implantation. O-Ray’s management has previously out-licensed three drug delivery products to larger pharmaceutical companies upon demonstration of proof-of-concept in the target patient populations.

项目摘要 自身免疫性内耳性疾病（AIED）是Deserder的名称 过度活跃的免疫系统，导致进行性听力丧失和/或头晕的症状。 AIED伴随着听力损失和耳鸣 迅速到第二只耳朵，表示AIE.3目前没有FDA批准的药物针对该主题 治疗AIED或任何类型的内耳听力损失。 抑制免疫功能的皮质类固醇是AIED的最常见治疗方法。 剂量的皮质类固醇会导致对这种未满足的医疗需求的显着副作用。 Pharma已开发了持续释放氟替卡松颗粒（OR-102）的铅配方进行处理 三个月内将为耳蜗提供皮质类固醇的aied。 将颗粒直接植入耳蜗，并在受影响的部位与类固醇相关，以防止 听力损失。 多个豚鼠研究。 为了测试OR-102在人类临床试验中的安全性和初步疗效， O-ray Pharma已向FDA提交了一个印度。 该申请的要求除了要进行额外的动物研究的请求，并建议其他 化学/制造/对照（CMC）作品。 临床方案和化学/制造/控制程序。 良好的实验室实践（GLP）的压缩症状和药代动力学研究 通讯为我们提供了一个清晰的框架，以实现这一目标的特定目的。 因此，直接到II阶段的建议是完成以下成分活动：1）药品 根据当前的良好制造实践（CGMP）制造动物和人类试验； 2）由FDA反馈指导的符合GLP的豚鼠研究的表现，3）准备和 提交IND回应。 INDD批准。 O射线的调查人员团队具有独特的资格，可以执行由Hrein进行的工作，并且 耳鼻喉，监管事务和业务发展方面的专业知识。 从概念到FDA批准开发了其他治疗配方 释放能够维持室内玻璃体内药物水平的类固醇植入物，最多三个Yeaars 从单个植入中 大型制药公司在目标人群中表现出概念验证后。