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.

受伤或手术的急性角膜疼痛可能很严重且使人衰弱。绷带隐形眼镜（BCLS）减轻角膜疼痛并促进伤口愈合，但不能充分治疗疼痛。结果，还规定了口服阿片类药物。不幸的是，口服阿片类药物与副作用有关，并导致了全国阿片类药物流行。由于这些原因，眼保健提供者和大多数患者都喜欢麻醉品。麻醉眼滴（例如四肌）可以挽救角膜疼痛，但由于可能归因于过度使用和滥用滴剂的可能性延迟伤口愈合，因此无法开处方进行自我管理。迄今为止，尚无OCULAR麻醉剂是FDA批准用于自我管理的。我们已经开发了一种麻醉的绷带隐形眼镜（A-BCL），该隐形眼镜（A-BCL）通过引入稀薄的药物聚合物膜来赋予四甲卡因的药物输送，该薄膜完全封装在典型的水凝胶CL的外围。可以通过更改药物聚合物膜的特性来调节发行轮廓。我们在兔子中的初步数据表明，最多可以减少30个小时的疼痛模拟，并且没有受损伤口愈合的证据。在我们实验室的经验的基础上，该应用的目标是通过以下目标完成必要的研究，以将A-BCL带入首次人类临床试验：AIM 1：优化，效率和A-BCL的表征。 AIM 2：A-BCL的药物分布，安全性和生物相容性。 AIM 3：使用A-BCL进行了GMP生产，IND申请的实施，以及向FDA提交IND申请，以进行首次人类临床试验。在AIM 1中，我们将在评估正常兔眼中效率的同时，将四卡因的释放持续时间从一天增加到两天。我们还将进行表征研究，以确保A-BCL符合绷带隐形眼镜的可接受参数。从这些研究中，我们将选择一个A-BCL公式，该公式将用于AIM 2用于药物分布，生物相容性研究和使用角膜上皮伤口愈合的兔模型。在AIM 3中，我们将完成将A-BCL生产到GMP设施的技术转移。在监管顾问（ORA）的指导下，我们将举行预定会议。一旦完成，我们将继续进行生物相容性研究，并完成IND应用，该应用将提交给FDA进行第一阶段I/II期临床试验。如果这些努力成功，患者将首次进行无阿片类药物治疗，以治疗严重的角膜疼痛。