Safety and Efficacy Study of Sivelestat in Neuromyelitis Optica Spectrum Disorder

Official title

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

Overview

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.

Interventions

• Drug Sivelestat sodium hydrate
  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.

Primary outcome measures

• Incidence of adverse events [Time frame: 4 weeks]

Secondary outcome measures (12)

• 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. [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 6 days]
• Change from baseline in Expanded Disability Status Scale (EDSS) score at 4 weeks (Day 28). [Time frame: 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). [Time frame: 4 weeks]
• Change from baseline in Functional System (FS) domain scores at 4 weeks [Time frame: 4 weeks]
• Change from baseline in Opticospinal Impairment Scale (OSIS) score at 4 weeks (Day 28). [Time frame: 4 weeks]
• Proportion of participants with recovery to pre-relapse neurological disability status at 4 weeks (Day 28). [Time frame: 4 weeks]
• Change from baseline in best-corrected visual acuity at 4 weeks (Day 28) [Time frame: 4 weeks]
• Change from baseline in critical flicker fusion frequency at 4 weeks (Day 28). [Time frame: 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). [Time frame: 4 weeks]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07738952 · CTR542-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗