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.
Přehled studie
Postavení
Intervence / Léčba
Typ studie
Zápis (Odhadovaný)
Fáze
- Fáze 2
- Fáze 1
Kontakty a umístění
Studijní kontakt
- Jméno: Mitsuru Watanabe, MD, PhD
- Telefonní číslo: +81926425340
- E-mail: shinkein@med.kyushu-u.ac.jp
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Popis
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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: N/A
- Intervenční model: Přiřazení jedné skupiny
- Maskování: Žádné (otevřený štítek)
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
|---|---|
|
Experimentální: Silelestat
|
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.
|
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Časové okno |
|---|---|
|
Výskyt nežádoucích jevů
Časové okno: 4 týdny
|
4 týdny
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
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.
Časové okno: 6 days
|
6 days
|
|
|
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.
Časové okno: 6 days
|
6 days
|
|
|
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.
Časové okno: 6 days
|
6 days
|
|
|
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.
Časové okno: 6 days
|
6 days
|
|
|
Change from baseline in Expanded Disability Status Scale (EDSS) score at 4 weeks (Day 28).
Časové okno: 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).
Časové okno: 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
Časové okno: 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.
|
4 weeks
|
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Change from baseline in Opticospinal Impairment Scale (OSIS) score at 4 weeks (Day 28).
Časové okno: 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).
Časové okno: 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
|
|
Change from baseline in best-corrected visual acuity at 4 weeks (Day 28)
Časové okno: 4 weeks
|
4 weeks
|
|
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Change from baseline in critical flicker fusion frequency at 4 weeks (Day 28).
Časové okno: 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).
Časové okno: 4 weeks
|
4 weeks
|
|
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Proportion of cases with gadolinium-enhancing lesions on MRI at 4 weeks.
Časové okno: 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.
Časové okno: 4 weeks
|
4 weeks
|
Spolupracovníci a vyšetřovatelé
Sponzor
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
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