Phase 1 Iontophoretic Delivery of Dexamethasone for Tx of Anterior Scleritis

摘要 非传染性巩膜炎是一种眼壁(巩膜)炎症性疾病。据估计， 美国的流行率为50,000。硬膜炎通常用口服非类固醇药物治疗。 炎性药物、全身皮质类固醇和/或全身免疫抑制 毒品。在三级环境中，大多数患者需要长期治疗，包括全身治疗。 皮质类固醇和/或免疫抑制。即使在系统性疾病的背景下， 硬化症经常驱使治疗方案。对于这种影响很大的孤儿疾病， 有效的局部给药治疗方案，避免全身副作用 将是非常可取的。 该提案要求提供资金，以便对离子导入传递进行初步评价。 地塞米松治疗非感染性、非坏死性巩膜炎，由IND进行。 EyeGate Pharma正在开发一种离子导入系统，以提供 地塞米松磷酸眼液(40毫克/毫升)滴眼，靶向 葡萄膜炎和干眼症的症状。地塞米松是一种众所周知的皮质类固醇， 几十年来可用于眼部和全身给药的其他配方。我们 认为离子导入皮质类固醇治疗可能有效 硬膜炎，因为它提供了一种将药物输送到结膜下的途径 血管丛，可迅速清除眼药水。现有证据表明 离子导入地塞米松治疗巩膜炎可能有效，包括： 全身性皮质类固醇和库皮质类固醇的有效性 治疗巩膜炎的巩膜，以及皮质类固醇滴眼液的部分疗效。不是 42名葡萄膜炎患者发生了限制发育的不良事件 105例干眼症患者参加评价离子导入给药的研究 地塞米松。 拟议中的研究--第一阶段，但不是第一次人类研究--将旨在评估安全性。 地塞米松离子导入治疗儿童前巩膜炎的耐受性 剂量变化研究。四组患者将被纳入并接受治疗。该药的剂量为 下一组将根据剂量的发生率增加或终止研究- 限制每一剂量的毒性。这项研究的主要目标是确定一系列 看起来安全和可耐受的剂量。次要目标是提供一个初步的 根据观察到的治疗反应和比例进行疗效评估 需要救援治疗。如果结果令人满意，该方法将在 第二阶段的研究正在计划中。

ABSTRACT Non-infectious scleritis is an inflammatory disease of the eye wall (sclera). Its estimated US prevalence is 50,000. 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 orphan disease, an effective locally administered treatment regimen that avoided systemic side effects would be very desirable. This proposal requests funding for an initial evaluation of iontophoretic delivery of dexamethasone for non-infectious, non-necrotizing scleritis, conducted under IND. Eyegate Pharma is developing an iontophor-etic delivery system to deliver dexamethasone phosphate ophthalmic solution (40 mg/mL) to the eye, targeting the indications of uveitis and dry eyes. Dexamethasone is a well-known corticosteroid, available in other formulations for ocular and systemic delivery for decades. We consider iontophoretic corticosteroid delivery as likely to be effective for treatment of scleritis, because it provides a means of delivering drug past the subconjunctival vascular plexus, which rapidly clears eyedrops. 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 eyedrops. 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-phase 1, but not first-in-human-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.