Subconjunctival Sirolimus for Active Anterior Scleritis (12-EI-0057)

这是一项I期、单中心、开放标签、非随机、前瞻性和非对照的初步研究，目的是评估结膜下注射西罗莫斯治疗活动性、自身免疫性、非坏死性、前部硬化症的安全性和可能的疗效。最初将纳入至少一个象限的5名活动期、自身免疫性、非坏死性、前部硬化性巩膜炎伴巩膜炎症分级为1+的参与者。参与者必须有需要口服非甾体抗炎药，或口服或局部应用皮质类固醇或免疫抑制药物的过往闪光史。最多可以登记七名参与者，因为最多可能积累两名参与者，以说明在收到任何调查产品之前退出研究的参与者。 如果两只眼是活动性的，首先注射炎症严重的那只眼(研究眼)，两周后注射第二只眼(对侧眼)。如果两只眼睛有相同的炎症反应，研究眼将在咨询参与者后由医生酌情选择。在最初的研究眼部注射后仍然表现出活动性炎症或发作的参与者可能有资格在第4周或之后再次注射(在8周内每只眼睛不超过1320克的剂量)。 主要结果是，根据NEI开发的标准化摄影巩膜炎分级系统，到第8周就诊时，经历至少两步减少或减少到研究眼巩膜炎症0级的参与者的数量。次要结果包括视力的变化，巩膜炎症的阶梯变化，经历疾病发作的参与者的数量，16周后从标准免疫抑制方案逐渐减少的参与者的数量，经历疾病发作的参与者中，从基线到疾病发作的天数，以及由于疾病发作而需要重新注射的参与者的数量。安全结果包括全身和眼部毒性和不良事件(AEs)的数量和严重程度，15篇早期治疗糖尿病视网膜病变研究(ETDRS)文献中经历视力丧失的参与者的比例，以及经历眼内压(IOP)大幅上升的参与者的数量。

This is a phase I, single-center, open-label, non-randomized, prospective and uncontrolled pilot study to evaluate the safety and possible efficacy of subconjunctival sirolimus injections for active, autoimmune, non-necrotizing, anterior scleritis.Five participants with active, autoimmune, non-necrotizing, anterior scleritis with scleral inflammatory grade of 1+ in at least one quadrant will be initially enrolled. Participants must have a history of past flares requiring oral NSAIDS, or oral or topical corticosteroids or immunosuppressive medication. Up to seven participants may be enrolled, as up to two participants may be accrued to account for participants who withdraw from the study prior to receiving any investigational product. If two eyes are active, the eye with worse inflammation will be injected first (study eye) at baseline followed two weeks later with injection of the second eye (fellow eye). If both eyes have equal inflammation, the study eye will be chosen at the physicians discretion after consultation with the participant. Participants that still demonstrate active inflammation or experience a flare-up after the initial study eye injection may be eligible for a re-injection at or after Week 4 (not to exceed a dose of 1,320 g per eye within an eight-week period). The primary outcome is the number of participants who experience at least a 2-step reduction or reduction to grade 0 of scleral inflammation in the study eye according to a standardized photographic scleritis grading system developed at NEI by the Week 8 visit. Secondary outcomes include changes in visual acuity, step changes in scleral inflammation, the number of participants who experience a disease flare, the number of participants tapered from the standard immunosuppressive regimen after 16 weeks and, of the participants who experience a disease flare, the number of days to disease flare from baseline as well as the number of participants who require re-injection due to a flare. Safety outcomes include the number and severity of systemic and ocular toxicities and adverse events (AEs), the proportion of participants who experience vision loss of 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).