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）： 非感染性巩膜炎是眼壁（巩膜）的炎性疾病。 巩膜炎通常使用口服非甾体类炎症药物、全身性皮质类固醇和/或全身性免疫抑制药物进行治疗。 在第三种情况下，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。 对于这种高影响的疾病，正在探索一种有效的局部给药治疗方案，避免全身副作用。 该提案要求提供资金，用于对地塞米松离子导入治疗非感染性、非坏死性巩膜炎进行初步评价。 目前正在开发一种将磷酸地塞米松眼用溶液（40毫克/毫升）输送到眼睛的离子电渗输送系统，该系统将针对葡萄膜炎和干眼的适应症。地塞米松是一种众所周知的皮质类固醇，数十年来可用于眼部和全身递送的其他制剂。离子电渗皮质类固醇给药可有效治疗巩膜炎，因为它提供了一种通过结膜下血管丛给药的方法，可快速清除滴眼液。现有证据表明，离子电渗递送地塞米松可能对巩膜炎有效，包括：全身性皮质类固醇和放置在巩膜附近的长效皮质类固醇对巩膜炎的有效性，以及皮质类固醇滴眼液的部分有效性。在42名葡萄膜炎患者和105名干眼患者中，没有遇到限制发育的不良事件，这些患者参加了评价地塞米松离子电渗给药的研究。拟定的研究是一项I期研究，但不是首次人体研究，旨在通过一项剂量变化研究评估地塞米松离子导入治疗前巩膜炎的安全性和耐受性。将入组并治疗4例患者。将增加下一组的剂量，否则将根据每个剂量下剂量限制性毒性的发生率终止研究。本研究的主要目的是确定一个安全和可耐受的剂量范围。次要目的是根据观察到的治疗反应和需要补救治疗的比例，提供疗效的初步评估。如果结果有利，则计划在II期研究中进一步开发该方法。