A Pilot Study to Investigate Ustekinumab (STELARA) for the Treatment of Active Sight-Threatening Uveitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 8
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing a Treatment Response by Week 16
研究概览
简要总结
Background:
Uveitis is an inflammation of the eye that can cause vision loss. It is treated with medications and sometimes surgery. However, in many people, treatment does not always prevent loss of vision. A new medication, ustekinumab, reduces inflammation in patients with other inflammatory diseases. Therefore, it might be helpful in treatment of uveitis.
Objective:
To see if ustekinumab is safe and can help people with uveitis.
Eligibility:
People ages 18 and older with uveitis
Design:
Participants will be screened with:
Medical and eye disease history
Physical exam
Eye exam: The pupil is dilated with eye drops. A machine scans the back of the eye. Pictures are taken of the inside of the eye.
Blood and urine tests
Tuberculosis test
Participants will have 6 clinic visits over 28 weeks. Visits lasts 2-3 hours and include:
- Medical and eye disease history
- Physical and eye exams
- Blood and urine tests
- Fluorescein angiography: A needle guides a thin plastic tube into an arm vein. A dye is injected into the tube. The dye travels through the veins up to the blood vessels in the eyes. A camera takes pictures of the dye as it flows through the blood vessels in the eyes.
- Cohort 1 - Ustekinumab injections at Weeks 0, 4, and 8: The injection is under the skin of the upper arm, leg, or abdomen.
Participants will have their uveitis monitored and receive standard uveitis care during the study.
- Cohort 2 - Ustekinumab injections via intravenous (IV) injection at first visit, followed by a single 90 mg injection of ustekinumab under the skin of the upper arm, leg or abdomen. For the IV injection a needle will be used to guide a thin plastic tube (catheter) into one of the arm veins. The needle will be removed, leaving only the catheter in the vein.
详细描述
Objective
Uveitis refers to intraocular inflammatory diseases that are an important cause of visual loss. Standard systemic immunosuppressive medications for uveitis can cause significant adverse effects and many patients continue to experience disease flare-ups. Ustekinumab is a human IL-12 and -23 antagonist. The involvement of IL-12 and IL-23 in the pathophysiology of uveitis and other autoimmune diseases known to be associated with uveitis suggests that ustekinumab could be a potential treatment for uveitis. The study objective is to investigate the safety, tolerability and potential efficacy of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis.
Study Population: The first cohort will consist of five participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. The second cohort will include up to four participants with active intermediate uveitis, posterior uveitis or panuveitis who meet the inclusion criteria. Up to eleven participants may be enrolled, as up to two participants may be accrued in the second cohort to account for participants who withdraw from the study prior to Week 16.
Design: This is a prospective, non-randomized, uncontrolled, two-arm pilot study to evaluate of ustekinumab as a possible treatment for active intermediate uveitis, posterior uveitis or panuveitis. Five participants in the first cohort will receive a 90 mg subcutaneous (SC) injection of ustekinumab at baseline and a second and third injection at Week 4 and 8 for a total of 3 injections. For the second cohort, up to four participants will receive an initial high, weight-based dose of ustekinumab via intravenous (IV) injection (up to 55 kg, 260 mg (2 vials); greater than 55 kg to 85 kg, 390 mg (3 vials); greater than 85 kg, 520 mg (4 vials)), followed by a single 90 mg subcutaneous injection at Week 8. In participants who demonstrate allergic reaction to the first dose, the second dose can also be administered as IV infusion with pre-infusion desensitization instead of a subcutaneous injection as it allows better control on the rate of drug administration. Participants will continue in the study for a total of 28 weeks and will be able to receive standard of care after the first 16 weeks.
Outcome Measures: For each cohort, the primary outcome is the number of participants who experience treatment response by Week 16. Secondary outcomes for each cohort include changes in visual acuity, the number of participants who experience a recurrence, the number of days to recurrence, presence or extent of macular edema, the amount of retino-vascular leakage, changes in retinal thickening, the length of time to quiescence and the ability to taper concomitant immunosuppressive medications. Safety outcomes for each cohort include the number and severity of systemic and ocular toxicities and adverse events, the proportion of participants who experience vision loss of greater than or equal to 15 letters as measured by Electronic Visual Acuity (EVA) and the number of participants who experience a substantial rise in elevated intraocular pressure (IOP).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
Cohort 1 (Subcutaneous Only)
Subcutaneous injections of Ustekinumab at baseline.
干预措施: Ustekinumab (Drug)
Cohort 2 (IV and Subcutaneous)
Initial IV infusion of ustekinumab at baseline followed by one subcutaneous injection at Week 8. In participants who demonstrate an allergic reaction to the baseline IV infusion, the second dose at Week 8 can also be administered as an IV infusion instead of a subcutaneous injection.
干预措施: Ustekinumab (Drug)
结局指标
主要结局
Number of Participants Experiencing a Treatment Response by Week 16
时间窗: Baseline to Week 16
The primary outcome is the number of participants in each cohort who experience a treatment response by Week 16. Treatment response is defined as experiencing all of the following for both/eligible eyes: no active inflammatory chorioretinal lesion and/or absent or decreased retinal vascular leakage; ≤ 0.5+ anterior chamber (AC) cells; ≤ 0.5+ vitreous haze.
次要结局
- Median Number of Days Until First Recurrence(Baseline to Week 16)
- Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)
- Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)
- Ability to Taper Concomitant Immunosuppressive Medications(Baseline to Week 28)
- Number of Participants Who Experience a Recurrence of Uveitis at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16)
- Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)
- Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Right Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Length of Time to Quiescence in the Right Eye(Baseline to Week 16)
- Mean Number of Days Until First Recurrence(Baseline to Week 16)
- Presence or Extent of Macular Edema as Determined by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)
- Amount of Retino-vascular Leakage as Measured by Fluorescein Angiogram (FA) in the Right Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)
- Length of Time to Quiescence in the Left Eye(Baseline to Week 16)
- Mean Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Changes in Central Retinal Thickness as Measured by Optical Coherence Tomography (OCT) in the Left Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Mean Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Median Change in Visual Acuity in the Right Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Median Change in Visual Acuity in the Left Eye at All Follow-up Visits Compared to Baseline(Baseline to Week 4, Week 8, Week 12, Week 16, Week 28)
- Presence or Extent of Macular Edema as Determined by Fluorescein Angiogram (FA) in the Left Eye at All Follow-up Visits(Week 4, Week 8, Week 12, Week 16, Week 28)