Safety and Efficacy Study of Sivelestat in Neuromyelitis Optica Spectrum Disorder (SIVAR-NMOSD)
A Phase I/IIa Investigator-Initiated Clinical Trial to Evaluate the Safety and Efficacy of Sivelestat in Patients With Acute Relapse of Neuromyelitis Optica Spectrum Disorder
The primary objective of this study is to evaluate the safety and tolerability of sivelestat sodium hydrate administered in combination with standard steroid pulse therapy in patients experiencing an acute NMOSD attack. Safety assessments will include adverse events, laboratory parameters, vital signs, and other clinically relevant findings. In addition, the study will explore whether the addition of sivelestat sodium hydrate to standard steroid pulse therapy improves neurological outcomes in patients with acute NMOSD.
Participants will receive intravenous sivelestat sodium hydrate at a dose of 4.8 mg/kg/day administered as a continuous infusion (0.2 mg/kg/hour) for 5 consecutive days, receive steroid pulse therapy according to the study protocol, and be followed for 28 days after treatment initiation for safety and efficacy evaluations.
研究概览
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名：Mitsuru Watanabe, MD, PhD
- 电话号码：+81926425340
- 邮箱：shinkein@med.kyushu-u.ac.jp
参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
Inclusion Criteria:
- Patients diagnosed with anti-AQP4 antibody-positive NMOSD according to the international diagnostic criteria for NMOSD (Wingerchuk, Neurology 2015).
Patients experiencing a relapse including any of the following, with the relapse occurring within 14 days of obtaining consent:
i. Unilateral or bilateral optic neuritis ii. Myelitis
- Patients whose FS domain has worsened by at least 1 point due to relapse.
- Patients with one or more relapse lesions identified on MRI (however, if the relapse is considered to have occurred in the same location as an existing MRI lesion neurologically, identification of a new relapse lesion is not required).
- Patients aged 18 years or older at the time of obtaining consent.
- Female patients of childbearing potential who agree to use appropriate contraception from the time of obtaining consent until 180 days after the end of investigational product administration.
- Male patients who agree to use appropriate contraception until 90 days after the end of investigational product administration.
- Patients who can provide written informed consent.
Exclusion Criteria:
- Patients with multi-organ dysfunction involving 4 or more organs.
- Patients with severe chronic respiratory disease.
- Patients with autoimmune diseases other than NMOSD that are expected to require additional treatment during the study period.
- Patients with active systemic bacterial, viral, or fungal infections.
Patients who have received either or both of the following prior treatments after an NMOSD relapse:
i. Two or more courses of steroid pulse therapy ii. Plasmapheresis iii. High-dose immunoglobulin therapy
- Patients with severe hepatic dysfunction.
- Patients with alcohol dependence, drug dependence, or psychiatric disorders that would interfere with study participation.
- Patients who have received other investigational drugs within 3 months prior to obtaining consent.
- Pregnant women, women suspected of being pregnant, or breastfeeding women.
- Patients with allergies to the investigational product or concomitant medications.
- Patients with severe allergies or a history of severe allergies.
Patients with suicidal tendencies meeting any of the following criteria:
i. Within 1 month prior to the screening assessment, there was suicidal behavior or ideation corresponding to "Yes" for Item 4 (Active suicidal ideation -some intent to act, but no specific plan) or Item 5 (Active suicidal ideation -specific plan and intent) of the Columbia-Suicide Severity Rating Scale (C-SSRS). (For subjects who only met Items 1-3, inclusion may be permitted at the discretion of the principal investigator or sub-investigator.) ii. Any suicidal behavior based on Item 6 of the C-SSRS occurred within the past 3 months.
- Other patients judged inappropriate by the principal investigator or sub-investigator.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：西维来司他
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Sivelestat sodium hydrate is administered intravenously at a dose of 4.8 mg/kg/day as a continuous infusion (0.2 mg/kg/hour) for 5 consecutive days in combination with steroid pulse therapy in patients with acute NMOSD attacks.
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研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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不良事件发生率
大体时间：4周
|
4周
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Change from baseline in body temperature at 3 hours, Day 2, Day 3, Day 4, Day 5, and Day 6 after the start of investigational product administration.
大体时间：6 days
|
6 days
|
|
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Change from baseline in blood pressure at 3 hours, Day 2, Day 3, Day 4, Day 5, and Day 6 after the start of investigational product administration.
大体时间：6 days
|
6 days
|
|
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Change from baseline in pulse rate at 3 hours, Day 2, Day 3, Day 4, Day 5, and Day 6 after the start of investigational product administration.
大体时间：6 days
|
6 days
|
|
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Change from baseline in percutaneous arterial oxygen saturation at 3 hours, Day 2, Day 3, Day 4, Day 5, and Day 6 after the start of investigational product administration.
大体时间：6 days
|
6 days
|
|
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Change from baseline in Expanded Disability Status Scale (EDSS) score at 4 weeks (Day 28).
大体时间：4 weeks
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The Expanded Disability Status Scale (EDSS) ranges from 0 to 10. Higher scores indicate greater neurological disability and worse clinical status.
|
4 weeks
|
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Proportion of cases where Expanded Disability Status Scale (EDSS) score improved by 1 point or more from baseline at 4 weeks (Day 28).
大体时间：4 weeks
|
The Expanded Disability Status Scale (EDSS) ranges from 0 to 10. Higher scores indicate greater neurological disability and worse clinical status.
|
4 weeks
|
|
Change from baseline in Functional System (FS) domain scores at 4 weeks
大体时间：4 weeks
|
Functional System (FS) scores are neurological disability scores that contribute to the Expanded Disability Status Scale (EDSS).
Functional systems assessed include visual, brainstem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral functions.
Individual FS scores generally range from 0 (normal function) to 5 or 6 (maximal impairment), depending on the functional system assessed.
Higher scores indicate greater neurological impairment and worse clinical status.
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4 weeks
|
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Change from baseline in Opticospinal Impairment Scale (OSIS) score at 4 weeks (Day 28).
大体时间：4 weeks
|
The Opticospinal Impairment Scale (OSIS) is a disability scale for neuromyelitis optica spectrum disorder that assesses visual acuity, motor function, sensory function, and sphincter function.
Total scores range from 0 to 25, with higher scores indicating greater neurological impairment and worse clinical status.
|
4 weeks
|
|
Proportion of participants with recovery to pre-relapse neurological disability status at 4 weeks (Day 28).
大体时间：4 weeks
|
Recovery to pre-relapse neurological disability status is defined as a return of the Expanded Disability Status Scale (EDSS; range 0-10, higher scores indicate greater disability) and the Opticospinal Impairment Scale (OSIS; range 0-25, higher scores indicate greater neurological impairment) to their respective pre-relapse scores.
|
4 weeks
|
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Change from baseline in best-corrected visual acuity at 4 weeks (Day 28)
大体时间：4 weeks
|
4 weeks
|
|
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Change from baseline in critical flicker fusion frequency at 4 weeks (Day 28).
大体时间：4 weeks
|
4 weeks
|
|
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Change from baseline in retinal nerve fiber layer and ganglion cell-inner plexiform layer thickness measured by optical coherence tomography (OCT) at 4 weeks (Day 28).
大体时间：4 weeks
|
4 weeks
|
|
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Proportion of cases with gadolinium-enhancing lesions on MRI at 4 weeks.
大体时间：4 weeks
|
4 weeks
|
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Proportion of cases requiring a second course of steroid pulse therapy, plasmapheresis, or high-dose immunoglobulin therapy.
大体时间：4 weeks
|
4 weeks
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合作者和调查者
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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