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、前瞻性和非对照的先导性研究，旨在评价结膜下注射西罗莫司治疗活动性、自身免疫性、非坏死性前巩膜炎的安全性和可能的疗效。最初将招募5名患有活动性、自身免疫性、非坏死性前巩膜炎且至少一个象限的巩膜炎症等级为1+的受试者。受试者必须有需要口服NSAIDS或口服或外用皮质类固醇或免疫抑制药物的既往发作史。最多可入组7名受试者，因为最多可累积2名受试者，以解释在接受任何试验用药物前退出研究的受试者。 如果两只眼睛是活动的，则在基线时首先注射具有更严重炎症的眼睛（研究眼睛），然后在两周后注射第二只眼睛（对侧眼睛）。如果两只眼睛的炎症程度相同，医生将在咨询受试者后自行决定选择研究眼。在首次研究眼部注射后仍表现出活动性炎症或经历突发的受试者可能有资格在第4周或之后再次注射（在8周内每只眼睛的剂量不超过1，320 g）。 主要结局是在第8周访视时，根据NEI开发的标准化摄影巩膜炎分级系统，研究眼的巩膜炎症经历至少2步减轻或减轻至0级的受试者数量。次要结局包括视力的变化、巩膜炎症的阶跃变化、经历疾病发作的受试者数量、16周后从标准免疫抑制方案逐渐减少的受试者数量、经历疾病发作的受试者、从基线到疾病发作的天数以及由于疾病发作需要重新注射的受试者数量。安全性结局包括全身和眼部毒性和不良事件（AE）的数量和严重程度，经历15个早期治疗糖尿病视网膜病变研究（ETDRS）字母的视力丧失的参与者比例，以及经历眼内压（IOP）升高大幅上升的参与者数量。

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).