Phase 1 Iontophoretic Delivery of Dexamethasone for Tx of Anterior Scleritis

地塞米松治疗前巩膜炎的 1 期离子电渗疗法

• 批准号: 8022593
• 负责人: JOHN H KEMPEN
• 金额: $ 17.43万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8022593
• 关键词: Phase; Iontophoretic; Delivery; Dexamethasone; Tx

DESCRIPTION (provided by applicant): Non-infectious scleritis is an inflammatory disease of the eye wall (sclera). Scleritis typically is managed with oral non-steroidal inflammatory drugs, systemic corticosteroids, and/or systemic immunosuppressive drugs. In tertiary settings, most patients require long-term therapy, including systemic corticosteroids and/or immunosuppression. Even in the context of systemic disease, scleritis often drives the treatment regimen. For this high impact disease, an effective locally administered treatment regimen that avoided systemic side effects is being explored. This proposal requests funding for an initial evaluation of iontophoretic delivery of dexamethasone for the treatment of non-infectious, non-necrotizing scleritis. An iontophoretic delivery system to deliver dexamethasone phosphate ophthalmic solution (40 milligrams/milliliter) to the eye is being developed and will target the indications of uveitis and dry eyes. Dexamethasone is a well-known corticosteroid, available in other formulations for ocular and systemic delivery for decades. Iontophoretic corticosteroid delivery may be an effective for treatment of scleritis as it provides a means of delivering drug past the subconjunctival vascular plexus, which rapidly clears eye drops. Available evidence suggesting that iontophoretically delivered dexamethasone may be effective for scleritis includes: effectiveness of systemic corticosteroids and depot corticosteroids placed adjacent to the sclera for scleritis, and partial effectiveness of corticosteroid eye drops. No development-limiting adverse events have been encountered in 42 uveitis patients and 105 dry eye patients enrolled in studies evaluating iontophoretic delivery of dexamethasone. The proposed study is a Phase 1, but not first-in-human study and will aim to assess the safety and tolerability of iontophoretic delivery of dexamethasone for anterior scleritis in a dose-varying study. Sets of four patients will be enrolled and treated. The dose for the next set will be increased or else the study terminated based on the incidence of dose limiting toxicity at each dose. The primary objective of this study is to identify a range of doses that appear safe and tolerable. The secondary objective is to provide a preliminary assessment of efficacy based on observed responses to treatment and the proportion requiring rescue therapy. If results are favorable, further development of the approach in Phase 2 studies is planned.

描述（由申请人提供）： 非感染性硬化症是眼壁（巩膜）的炎症性疾病。 巩膜炎通常用口服非甾体类炎症药，全身性皮质类固醇和/或全身免疫抑制药物来治疗。 在三级环境中，大多数患者需要长期治疗，包括全身性皮质类固醇和/或免疫抑制。即使在全身性疾病的背景下，巩膜炎也经常驱动治疗方案。 对于这种高影响疾病，正在探索一种有效的本地管理治疗方案，该治疗方案正在探索避免使用的全身副作用。 该提案要求资助对地塞米松的离子噬递送的初步评估，以治疗非感染，非肿瘤性硬化症。 开发了一种磷酸磷酸盐眼溶液（40毫克/毫克）的离子托管输送系统正在开发到眼睛，并将针对葡萄膜炎和干眼的指示。地塞米松是一种众所周知的皮质类固醇，可在其他用于眼和全身递送的配方中使用数十年。离子疗法皮质类固醇的递送可能有效地治疗硬化性巩膜炎，因为它提供了一种使药物超越膜下血管丛的方法，从而迅速清除眼部滴眼液。可用的证据表明，离子送交递的地塞米松可能对巩膜炎有效，包括：全身性皮质类固醇的有效性和与硬化症相邻的巩膜炎和皮质固醇眼睛滴的部分有效性的有效性。在42名葡萄膜炎患者和105名干眼患者中，没有遇到限制性不良事件，该研究评估了地塞米松的离子噬菌递送的研究。拟议的研究是第1阶段，但不是人类的第一阶段研究，旨在评估地塞米松在剂量变化的研究中递送地塞米松对前巩膜炎的安全性和耐受性。将入学和治疗四名患者的组。下一组的剂量将增加，否则该研究根据每种剂量限制毒性的发生率而终止。这项研究的主要目的是确定看起来安全可容忍的一系列剂量。次要目标是根据观察到的治疗反应以及需要救援治疗的比例来对疗效进行初步评估。如果结果有利，则计划在第二阶段研究中进一步发展该方法。