Gevokizumab Treatment for Active Scleritis By IL-1 Inhibition (GATSBY)

巩膜炎是一种慢性、疼痛和潜在致盲的炎症性疾病，以巩膜上和巩膜组织水肿为特征，通常与全身自身免疫性疾病有关。Gevokizumab是一种白介素1(IL-1)抑制剂，因此可能预防IL-1，这可能是导致前部巩膜炎患者巩膜破裂的原因。本研究的目的是评估Gevokizumab作为一种可能的治疗非感染性、活动性前巩膜炎的安全性和潜在疗效。 研究人群：10名非感染性、活动性、前部巩膜炎患者，至少一只眼巩膜炎症分级为+1，将最初纳入研究对象。然而，对于在第16周前退出研究的参与者，最多可以再招募两名参与者。参与者在注册时可能每天服用20毫克或等量的泼尼松，但所有其他免疫抑制药物将随着研究药物的开始而停用。 这是一项1/2期、开放标签、非随机、前瞻性、单臂试点试验，旨在评估Gevokizumab治疗非感染性、活动性前巩膜炎的安全性和潜在疗效。这项研究包括初始阶段和随后的扩展阶段。在初始阶段，所有参与者将在基线以及第4、8和12周接受一次60毫克的Gevokizumab皮下注射。在第16周，参与者将接受研究扩展阶段的资格评估。不继续研究扩展阶段的参与者将停止研究药物，并可由研究人员酌情使用标准护理治疗接受抢救治疗。没有继续延长阶段的参与者将在第28周返回进行最后一次安全访问。被确定为符合延长阶段条件的参与者可以继续进入延长阶段，并每四周接受一次Gevokizumab注射(60毫克)，直到第36周就诊。延期阶段的参与者将在第40周和第52周进行安全访问。 主要结果是，根据NEI开发的标准化摄影巩膜炎分级系统(见附录3)，与基线相比，在第16周就诊时或之前，研究眼(或双眼，如果双眼符合研究眼标准)的巩膜炎症至少减少或减少到0级的参与者数量。次要结果包括视力的改变、眼压的改变和巩膜分级的改变。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，以及参与者在任何后续访问中丢失15个ETDRS字母的比例。

Scleritis is a chronic, painful and potentially blinding inflammatory disease characterized by edema of the episcleral and sclera tissues and is commonly associated with systemic autoimmune disorders. Gevokizumab is an interleukin-1β (IL-1β) inhibitor, thus possibly preventing the IL-1β that may be responsible for scleral breakdown in patients with anterior scleritis. The study objective is to evaluate the safety and potential efficacy of gevokizumab as a possible treatment of non-infectious, active, anterior scleritis. Study Population: Ten participants with non-infectious, active, anterior scleritis with a scleral inflammatory grade of ≥ +1 in at least one eye will be initially enrolled. However, up to an additional two participants may be enrolled to account for participants who withdraw from the study prior to Week 16. Participants may be on ≤ 20 mg/day of prednisone or the equivalent at the time of enrollment but all other immunosuppressive drugs will be stopped with the initiation of study drug. This is a Phase 1/2, open label, non-randomized, prospective, single-arm, pilot trial to evaluate the safety and potential efficacy of gevokizumab in non-infectious, active, anterior scleritis. The study consists of an initial phase followed by an extension phase. For the initial phase, all participants will receive one subcutaneous injection of 60 mg gevokizumab at Baseline and Weeks 4, 8 and 12. At Week 16, participants will be assessed for eligibility in the extension phase of the study. Participants who do not continue in the extension phase of the study will discontinue the study drug and may receive salvage therapy using standard-of-care treatment at the investigators discretion. Participants who do not continue in the extension phase will return for a final safety visit at Week 28. Participants who are determined eligible for the extension phase may continue in the extension phase and receive one gevokizumab injection (60 mg) every four weeks until the Week 36 visit. Participants in the extension phase will have safety visits at Weeks 40 and 52. The primary outcome is the number of participants with at least a 2-step reduction or reduction to grade 0 in scleral inflammation in the study eye (or eyes, if both eyes meet study eye criteria), according to a standardized photographic scleritis grading system developed at NEI (see Appendix 3), on or before the Week 16 visit as compared to Baseline. Secondary outcomes include changes in visual acuity, changes in intraocular pressure and changes in scleral grading. Safety outcomes include the number and severity of systemic and ocular toxicities and adverse events (AEs), and the proportion of participants with loss of ≥ 15 ETDRS letters at any follow-up visit.