Gevokizumab Treatment for Active Scleritis By IL-1 Inhibition (GATSBY)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 2
- 主要终点
- Number of Participants With at Least a 2-step Reduction or Reduction to Grade 0 in Scleral Inflammation in the Study Eye (or Eyes), According to the National Eye Institute (NEI) Photographic Scleritis Grading System, on or Before the Week 16 Visit.
研究概览
简要总结
Background:
- Scleritis is the inflammation of the white outer coating of the eye, known as the sclera. In severe cases, it can cause blindness. It is commonly associated with autoimmune disorders such as rheumatoid arthritis. Mild scleritis can be treated with drugs such as ibuprofen. More severe scleritis may need oral steroids or immunosuppressive treatments; however, these treatments can cause side effects in the whole body. Gevokizumab is a newer anti-inflammatory drug that is under investigation to treat other inflammatory diseases. It may not have as severe side effects as some other drugs. However, it has not yet been used to treat scleritis. Researchers want to see if it can be given as a safe and effective treatment for scleritis.
Objectives:
- To see if gevokizumab is a safe and effective treatment for scleritis.
Eligibility:
- Individuals at least 18 years of age who have active scleritis.
Design:
- There is an initial phase and a two-part extension phase in this study. The extension phase is optional. The initial phase of the study requires seven visits to the National Eye Institute (NEI).
- Participants will be screened with a physical exam and eye exam, and medical history will be obtained. Blood and urine samples will be collected.
- Eligible participants will receive an injection of 60 mg of gevokizumab at the first study visit and at Weeks 4, 8, and 12. They will be given under the skin by the stomach, or in the upper arm or thigh.
- Participants will have additional visits after the first study visit at Weeks 2, 16, and 28. No injection will be given at these visits. Eye exams will be done, and blood and tear samples will be collected.
- If the scleritis improves by Week 16, participants may choose to continue the study in the extension phase. In the 1st extension, they will have a visit every 4 weeks until Week 36 and then two additional monitoring visits at Weeks 40 and 52 for a total of 13 study visits.
- Participants who are eligible at Week 52 may continue in the "as needed" (PRN) extension phase (2nd extension) and receive gevokizumab injections (60 mg) at Weeks 52, 54, 58 and 62.
详细描述
Objective
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 were to be initially enrolled. However, only eight participants were enrolled. 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.
Design: 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 a two-part 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 of the initial phase, participants will be assessed for eligibility in the first extension phase of the study. Participants from the initial phase, who do not continue in the first extension phase of the study will discontinue the study drug and may receive salvage therapy using standard-of-care treatment at the investigator's discretion. Participants from the initial phase who do not continue in the first extension phase will return for a final safety visit at Week 28. Participants from the initial phase who are determined eligible for the first extension phase may continue in the first extension phase and receive one gevokizumab injection (60 mg) every four weeks until the Week 36 visit. Participants entering the first extension phase will have follow-up safety visits at Weeks 40 and 52. At Week 52 follow-up of the first extension phase, participants will be assessed for eligibility in the 2nd extension phase, which is a PRN extension phase of the study. Participants who are eligible may continue in the PRN extension phase (2nd extension) and receive gevokizumab injections (60 mg) at Weeks 52, 54, 58, and 62. Subjects that have already completed the week 52 visit will be eligible to return and be assessed for entry into this 2nd extension phase. If they have already completed the Week 52 exit visit from the protocol and are returning to enroll in the PRN extension phase (2nd extension), the visits will be labeled as Weeks 52 (PRN-week0), 54 (PRN-week2), 58 (PRN-week6), and 62 (PRN-week10). Participants in the PRN extension phase (2nd extension) will have a final safety visit at least 16 weeks following their last injection in the PRN extension phase (2nd extension).
Outcome Measures: 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, 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.
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
Gevokizumab
Subcutaneous injection of 60 mg gevokizumab
干预措施: Gevokizumab (Device)
结局指标
主要结局
Number of Participants With at Least a 2-step Reduction or Reduction to Grade 0 in Scleral Inflammation in the Study Eye (or Eyes), According to the National Eye Institute (NEI) Photographic Scleritis Grading System, on or Before the Week 16 Visit.
时间窗: Baseline and Week 16
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
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 40 Compared to Baseline(Baseline and Week 40)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 12 Compared to Baseline(Baseline and Week 12)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 4 Compared to Baseline(Baseline and Week 4)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 8 Compared to Baseline(Baseline and Week 8)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 16 Compared to Baseline(Baseline and Week 16)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 24 Compared to Baseline(Baseline and Week 24)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 52 Compared to Baseline(Baseline and Week 52)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 8 Compared to Baseline(Baseline and Week 8)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 12 Compared to Baseline(Baseline and Week 12)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 40 Compared to Baseline(Baseline and Week 40)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 52 Compared to Baseline(Baseline and Week 52)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 2 Compared to Baseline(Baseline and Week 2)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 20 Compared to Baseline(Baseline and Week 20)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 32 Compared to Baseline(Baseline and Week 32)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 36 Compared to Baseline(Baseline and Week 36)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 52A Compared to Baseline(Baseline and Week 52A)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 58 Compared to Baseline(Baseline and Week 58)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 20 Compared to Baseline(Baseline and Week 20)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 28 Compared to Baseline(Baseline and Week 28)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 54 Compared to Baseline(Baseline and Week 54)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Final Safety Visit Compared to Baseline(Baseline and Final Visit)
- Mean Change in Visual Acuity in the Study Eye (or Eyes) at Week 62 Compared to Baseline(Baseline and Week 62)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 16 Compared to Baseline(Baseline and Week 16)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 54 Compared to Baseline(Baseline and Week 54)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 28 Compared to Baseline(Baseline and Week 28)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 32 Compared to Baseline(Baseline and Week 32)
- Changes in Scleral Grading From Baseline to Week 52(Baseline and Week 52)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 2 Compared to Baseline(Baseline and Week 2)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 4 Compared to Baseline(Baseline and Week 4)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 24 Compared to Baseline(Baseline and Week 24)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 52A Compared to Baseline(Baseline and Week 52A)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 58 Compared to Baseline(Baseline and Week 58)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 36 Compared to Baseline(Baseline and Week 36)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Week 62 Compared to Baseline(Baseline and Week 62)
- Mean Change in Intraocular Pressure in the Study Eye (or Eyes) at Final Safety Visit Compared to Baseline(Baseline and Final Visit)
- Number of Participants With Loss of ≥ 15 Early Treatment Diabetic Retinopathy Study (ETDRS) Letters(Post-injection through study completion, up to 78 weeks per participant)