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.
Обзор исследования
Статус
Вмешательство/лечение
Тип исследования
Регистрация (Оцененный)
Фаза
- Фаза 2
- Фаза 1
Контакты и местонахождение
Контакты исследования
- Имя: Mitsuru Watanabe, MD, PhD
- Номер телефона: +81926425340
- Электронная почта: shinkein@med.kyushu-u.ac.jp
Критерии участия
Критерии приемлемости
Возраст, подходящий для обучения
- Взрослый
- Пожилой взрослый
Принимает здоровых добровольцев
Описание
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.
Учебный план
Как устроено исследование?
Детали дизайна
- Основная цель: Уход
- Распределение: Н/Д
- Интервенционная модель: Одногрупповое задание
- Маскировка: Нет (открытая этикетка)
Оружие и интервенции
Группа участников / Армия |
Вмешательство/лечение |
|---|---|
|
Экспериментальный: Сивелестат
|
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.
|
Что измеряет исследование?
Первичные показатели результатов
Мера результата |
Временное ограничение |
|---|---|
|
Частота нежелательных явлений
Временное ограничение: 4 недели
|
4 недели
|
Вторичные показатели результатов
Мера результата |
Мера Описание |
Временное ограничение |
|---|---|---|
|
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.
Временное ограничение: 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.
Временное ограничение: 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.
Временное ограничение: 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.
Временное ограничение: 6 days
|
6 days
|
|
|
Change from baseline in Expanded Disability Status Scale (EDSS) score at 4 weeks (Day 28).
Временное ограничение: 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
|
|
Proportion of cases where Expanded Disability Status Scale (EDSS) score improved by 1 point or more from baseline at 4 weeks (Day 28).
Временное ограничение: 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
Временное ограничение: 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
|
|
Change from baseline in Opticospinal Impairment Scale (OSIS) score at 4 weeks (Day 28).
Временное ограничение: 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).
Временное ограничение: 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)
Временное ограничение: 4 weeks
|
4 weeks
|
|
|
Change from baseline in critical flicker fusion frequency at 4 weeks (Day 28).
Временное ограничение: 4 weeks
|
4 weeks
|
|
|
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).
Временное ограничение: 4 weeks
|
4 weeks
|
|
|
Proportion of cases with gadolinium-enhancing lesions on MRI at 4 weeks.
Временное ограничение: 4 weeks
|
4 weeks
|
|
|
Proportion of cases requiring a second course of steroid pulse therapy, plasmapheresis, or high-dose immunoglobulin therapy.
Временное ограничение: 4 weeks
|
4 weeks
|
Соавторы и исследователи
Спонсор
Даты записи исследования
Изучение основных дат
Начало исследования (Оцененный)
Первичное завершение (Оцененный)
Завершение исследования (Оцененный)
Даты регистрации исследования
Первый отправленный
Впервые представлено, что соответствует критериям контроля качества
Первый опубликованный (Действительный)
Обновления учебных записей
Последнее опубликованное обновление (Действительный)
Последнее отправленное обновление, отвечающее критериям контроля качества
Последняя проверка
Дополнительная информация
Термины, связанные с этим исследованием
Ключевые слова
Другие идентификационные номера исследования
- CTR542-01
Планирование данных отдельных участников (IPD)
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Информация о лекарствах и устройствах, исследовательские документы
Изучает лекарственный продукт, регулируемый FDA США.
Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.
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