A Phase I/II Study to Investigate Subconjunctival Sirolimus for the Treatment of Active Autoimmune Non-Necrotizing Anterior Scleritis
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Number of Participants Who Experience at Least 2-step Reduction or Reduction to Grade 0 of Scleral Inflammation in the Study Eye According to the National Eye Institute (NEI) Photographic Scleritis Grading System Within 8 Weeks Post-injection.
研究概览
简要总结
Background:
Autoimmune scleritis is an inflammatory disease that affects the white outer part of the eye. It is associated with immune system disorders like rheumatoid arthritis. It can cause blindness in severe cases. Most treatments for scleritis involve steroid or immune-suppressing drugs, but these can cause side effects in the whole body.
Sirolimus is a drug used to help prevent transplant rejection. It helps prevent the immune system from attacking the body. Researchers want to try giving sirolimus injections into the eye to treat severe scleritis.
Objectives:
To see if sirolimus is a safe and effective treatment for autoimmune scleritis.
Eligibility:
Individuals at least 18 years of age with autoimmune scleritis in at least one eye that has not responded to standard treatments.
Design:
- Participants will be screened with a medical history, physical exam, and eye exam. Blood and urine samples will also be collected.
- One eye will be selected as the study eye to receive injections.
- Participants will have six study visits over 4 months (initial visit and weeks 2, 4, 8, 12, and 16). The injection will be given at the first visit. If the study eye responds to the treatment, participants may have injections in the other eye at the second visit.
- If there is still inflammation after the first injection, or if the scleritis improves but then returns, participants may have a second injection at Week 4.
- Injections will be monitored with blood tests and eye exams.
- Participants may have study visits and injections for up to 1 year if the injections seem to be working.
详细描述
OBJECTIVE:
Scleritis is a chronic, painful and potentially blinding inflammatory disease characterized by edema of the episcleral and scleral tissues and is commonly associated with systemic autoimmune disorders. Sirolimus suppresses cytokine-driven T-cell proliferation and thus, inhibits the production, signaling and activity of many growth factors relevant to scleritis. Subconjunctival sirolimus administration could reduce or eliminate the need for topical and/or systemic immunosuppressive drugs often taken with immunosuppressive disorders that could result in reduced morbidity. The study objective is to investigate the safety, tolerability and potential efficacy of subconjunctival sirolimus as a possible treatment for active, autoimmune, non-necrotizing, anterior scleritis.
STUDY POPULATION:
Five participants with active, autoimmune, non-necrotizing, anterior scleritis with scleral inflammatory grade ≥ 1+ in at least one quadrant will be initially enrolled. Participants must have a history of past flares requiring oral non-steroidal anti-inflammatory drugs (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.
DESIGN:
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Sirolimus
Participants will receive a15 μL (660 μg) subconjunctival injection of sirolimus in the study eye at baseline if a single quadrant or two adjacent quadrants are involved. If greater than two quadrants are involved (i.e., 3 or 4 quadrant involvement) or two non-adjacent quadrants are involved, two 15 μL (660 μg) injections will be given in two quadrants 180 degrees apart (total dose of 30 μL or 1,320 μg). Participants that still demonstrate active inflammation (incomplete or no response to initial injection) or experience a flare-up (as defined by a ≥1-step increase in scleral inflammation) after the initial injection will be eligible for a re-injection in the study eye at or after Week 4 (not to exceed a dose of 1,320 μg per eye within an eight-week period).
干预措施: Sirolimus (Drug)
结局指标
主要结局
Number of Participants Who Experience at Least 2-step Reduction or Reduction to Grade 0 of Scleral Inflammation in the Study Eye According to the National Eye Institute (NEI) Photographic Scleritis Grading System Within 8 Weeks Post-injection.
时间窗: Baseline and Week 8
The primary efficacy outcome was a 2-step reduction in scleritis grading out of a scale of 0 to 4+ (where 0.5+ is recognized as an ordinal step between 1+ and 0+). Scleral inflammation was graded following 10% Phenylephrine application with an ordinal scale of 0 (no scleral inflammation with complete blanching of vessels), 0.5+ (minimal/trace inflammation with localized pink appearance of the sclera around minimally dilated deep episcleral vessels), 1+ (mild inflammation with diffuse pink appearance of the sclera around mildly dilated deep episcleral vessels), 2+ (moderate inflammation with purplish pink appearance of the sclera with tortuous and engorged deep episcleral vessels), 3+ (severe inflammation with diffuse significant redness of sclera, the details of superficial and deep episcleral vessels can't be observed), and 4+ (necrotizing inflammation with diffuse redness of the sclera with scleral thinning and uveal show).
次要结局
- Number of Participants Who Experience a Disease Flare as Defined by a ≥ 1-step Increase in Scleral Inflammation(Baseline and Week 52)
- Mean Change in Visual Acuity Via the Early Treatment Diabetic Retinopathy Study (ETDRS)(Baseline and Week 52)
- Number of Participants Who Tapered Off One or More Systemic Immunosuppressive Medications or Tapered Off Prednisone (≤10 mg) After Week 16(Week 16 and Week 52)
- Proportion of Participants With Loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters(Baseline to Week 52)
- Number of Participants Who Experience a Substantial Rise in Elevated Intraocular Pressure (IOP)(Baseline and Week 52)
- Step Changes in Scleral Inflammation According to the Standardized Photographic Grading System Developed at National Eye Institute (NEI)(Baseline and Week 52)
- Mean Number of Days Between the First Injection to the Second Injection(Baseline and Week 52)
- Median Change in Visual Acuity Via the Early Treatment Diabetic Retinopathy Study (ETDRS)(Baseline and Week 52)
- Number of Participants Needing a Second Injection(Baseline and Week 52)
- Number of Participants Who Experienced Ocular Toxicities(Baseline and Week 52)
- Number of Participants Who Experienced Systemic Toxicities(Baseline and Week 52)