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.
調査の概要
研究の種類
入学 (推定)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究連絡先
- 名前：Mitsuru Watanabe, MD, PhD
- 電話番号：+81926425340
- メール：shinkein@med.kyushu-u.ac.jp
参加基準
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
説明
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.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的：シベレスタット
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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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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
時間枠 |
|---|---|
|
有害事象の発生率
時間枠：4週間
|
4週間
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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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.
時間枠：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.
時間枠：6 days
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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.
時間枠：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.
時間枠：6 days
|
6 days
|
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Change from baseline in Expanded Disability Status Scale (EDSS) score at 4 weeks (Day 28).
時間枠：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
|
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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).
時間枠：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
時間枠：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).
時間枠：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
|
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Proportion of participants with recovery to pre-relapse neurological disability status at 4 weeks (Day 28).
時間枠：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.
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4 weeks
|
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Change from baseline in best-corrected visual acuity at 4 weeks (Day 28)
時間枠：4 weeks
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4 weeks
|
|
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Change from baseline in critical flicker fusion frequency at 4 weeks (Day 28).
時間枠：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).
時間枠：4 weeks
|
4 weeks
|
|
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Proportion of cases with gadolinium-enhancing lesions on MRI at 4 weeks.
時間枠：4 weeks
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4 weeks
|
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Proportion of cases requiring a second course of steroid pulse therapy, plasmapheresis, or high-dose immunoglobulin therapy.
時間枠：4 weeks
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4 weeks
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協力者と研究者
スポンサー
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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