Anesthetic-Eluting Contact Lens for Corneal Pain

用于治疗角膜疼痛的麻醉洗脱隐形眼镜

• 批准号: 10646991
• 负责人: Joseph B. Ciolino
• 金额: $ 112.09万
• 依托单位: SCHEPENS EYE RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10646991
• 关键词: Acute; Address; Anesthetics; Bandage; Characteristics; Clinical; Clinical Trials; Contact Lenses; Cornea; Corneal Abrasion; Corneal pain; Cystoid Macular Edema; Data; Dexamethasone; Dose; Drops; Drug Delivery Systems; Drug Kinetics; Encapsulated; Ensure; Eye; Eyedrops; FDA approved; Fentanyl; Film; Formulation; Funding; Future; Glaucoma; Goals; Grant; Hour; Human; Hydrogels; Impaired wound healing; In Vitro; Industry; Injury; Institutional Review Boards; Laboratories; Latanoprost; Lead; Medical; Modeling; Monitor; Narcotics; Operative Surgical Procedures; Ophthalmologist; Opioid; Oral; Oryctolagus cuniculus; Pain; Patients; Permeability; Pharmaceutical Preparations; Pharmacologic Substance; Phase I/II Clinical Trial; Polymers; Procedures; Production; Recurrence; Research; Research Contracts; Research Personnel; Review Committee; Risk; Safety; Self Administration; Specialist; Technology; Technology Transfer; Tetracaine; Therapeutic; Thinness; Time; Tissues; Toxic effect; Toxicology; Translating; Trauma; United States; Vision; Water; Wound models; abuse liability; addiction; biomaterial compatibility; care providers; corneal epithelial wound healing; drug distribution; effective therapy; efficacy evaluation; efficacy study; experience; first-in-human; human study; in vivo; interest; laboratory experience; lens; light transmission; manufacturing technology; melting; member; multidisciplinary; ocular surface; opioid epidemic; pain reduction; pain relief; physical property; pre-Investigational New Drug meeting; preclinical study; prescription opioid; randomized, clinical trials; side effect; standard of care; wound healing

Acute corneal pain from injury or surgery can be severe and debilitating. Bandage contact lenses (BCLs) mitigate corneal pain and promote wound healing, but do not sufficiently treat the pain. As a result, oral opioids are also prescribed. Unfortunately, oral opioids are associated with side effects and have contributed to the nationwide opioid epidemic; for these reasons eye care providers and most patients prefer narcotics. Anesthetic eye drops, such as tetracaine, can relieve corneal pain, but cannot be prescribed for self-administration due to the potential for delayed wound healing that has been attributed to overuse and abuse of the drops. To date, NO ocular anesthetics are FDA-approved for self-administration. We have developed an anesthetic-eluting bandage contact lens (A-BCL) that enables controlled drug delivery of tetracaine by introducing a thin drug-polymer film that is fully encapsulated within the periphery of a typical hydrogel CL. The release profile can be modulated by changing the characteristics of the drug polymer film. Our preliminary data in rabbits demonstrates up to 30 hours of reduced pain stimulation and no evidence of compromised wound healing. Building on our laboratory’s experience, the goal of this application is to complete the necessary studies to bring the A-BCL to a first-in-human clinical trial through the following Aims: Aim 1: Optimization, efficacy, and characterization of A-BCLs. Aim 2: Drug distribution, safety, and biocompatibility of A-BCLs. Aim 3: Implementation of GMP production, Pre-IND meeting, and submission of IND application to the FDA for a first-in-human clinical trial using A-BCLs. In Aim 1, we will increase the duration of tetracaine release from one to two days while evaluating efficacy in normal rabbit eyes. We will also conduct characterization studies to ensure the A-BCL meets acceptable parameters for bandage contact lenses. From these studies, we will choose a A-BCL formulation, which will be used in Aim 2 for drug distribution, biocompatibility studies, and safety using a rabbit model of corneal epithelial wound healing. In Aim 3, we will complete technology transfer of A-BCL production to a GMP facility. With guidance from regulatory consultants (ORA), we will conduct a Pre-IND meeting. Once this is complete, we will proceed with our biocompatibility studies and complete an IND application that will be submitted to the FDA for a first-in-human Phase I/II clinical trial. If these efforts are successful, patients will have, for the first time, an opioid-free treatment for severe corneal pain.

受伤或手术引起的急性角膜疼痛可能会很严重并且使人衰弱。绷带隐形眼镜 (BCL) 可减轻角膜疼痛并促进伤口愈合，但不能充分治疗疼痛。因此，还开了口服阿片类药物。不幸的是，口服阿片类药物具有副作用，并导致全国阿片类药物流行；由于这些原因，眼科护理人员和大多数患者更喜欢使用麻醉剂。丁卡因等麻醉滴眼液可以缓解角膜疼痛，但不能自行给药，因为过度使用和滥用滴眼液可能会延迟伤口愈合。迄今为止，FDA 尚未批准任何一种可自行给药的眼部麻醉剂。 我们开发了一种麻醉洗脱绷带隐形眼镜 (A-BCL)，通过引入完全封装在典型水凝胶 CL 外围的药物聚合物薄膜，可以控制丁卡因的药物输送。可以通过改变药物聚合物膜的特性来调节释放曲线。我们对兔子的初步数据表明，疼痛刺激可减少长达 30 小时，并且没有证据表明伤口愈合受损。基于我们实验室的经验，本申请的目标是完成必要的研究，通过以下目标将 A-BCL 进行首次人体临床试验： 目标 1：A-BCL 的优化、功效和表征。目标 2：A-BCL 的药物分布、安全性和生物相容性。目标 3：实施 GMP 生产、召开 IND 前会议，并向 FDA 提交 IND 申请，以进行使用 A-BCL 的首次人体临床试验。 在目标 1 中，我们将丁卡因的释放持续时间从 1 天延长至 2 天，同时评估对正常兔眼的疗效。我们还将进行特性研究，以确保 A-BCL 满足绷带隐形眼镜可接受的参数。从这些研究中，我们将选择一种 A-BCL 制剂，该制剂将用于目标 2 中，使用兔角膜上皮伤口愈合模型进行药物分布、生物相容性研究和安全性。在目标3中，我们将完成A-BCL生产向GMP设施的技术转移。在监管顾问（ORA）的指导下，我们将举行预 IND 会议。一旦完成，我们将继续进行生物相容性研究并完成 IND 申请，该申请将提交给 FDA 进行首次人体 I/II 期临床试验。如果这些努力取得成功，患者将首次接受不含阿片类药物的严重角膜疼痛治疗。