Overview
This is a single-center, randomized, open-label, placebo-controlled, dose-escalation trial. The objective of this research is to evaluate the safety, tolerability, and efficacy of intrathecal administration of human-induced neural stem cell-derived extracellular vesicles (NouvSoma001) for the treatment of neuromyelitis optica spectrum disorders.
Description
This is a single-center, randomized, open-label, placebo-controlled, dose-escalation trial. The study consists of two parts: Part 1 is a dose-escalation study, while Part 2 is a dose-extension study based on the results of Part 1. Part 1 will follow a traditional 3+3 dose-escalation design, enrolling a total of 9 subjects. In Cohort 1, participants will receive 5 × 10^9 particles; in Cohort 2, they will receive 1.5 × 10^10 particles; and in Cohort 3, they will receive 3 × 10^10 particles. If no dose-limiting toxicities (DLTs) are observed within 2 weeks after the initial administration, a new cohort will be enrolled at the next higher dose level. If DLTs are observed in 1 participant, another 2 participants will be treated at the same dose level. Dose escalation will cease if DLTs are observed in more than 33% of the participants. In Part 2, the remaining 60 participants will be randomized in a 2:1 ratio to the treatment and placebo groups, with the dose level determined by the Data Safety Monitoring Board based on the results of Part 1.
Eligibility
Inclusion Criteria:
- Patients must meet the 2015 International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) and test positive for AQP4 antibodies.
- Symptom onset occurred within 7 days prior to enrollment, with associated severe pain, lower limb motor dysfunction, or urinary/bowel impairment.
- Males or Females aged between 18 and 65 years.
- The Expanded Disability Status Scale (EDSS) score prior to the current disease episode is ≤ 4.
- Female participants of childbearing potential must present a negative pregnancy test at screening and agree to use effective contraception throughout the study period.
- Informed consent must be obtained from the patient or their legal representative, with a signed consent form must be provided.
Exclusion Criteria:
- Abnormal laboratory indicators of the subjects need to be excluded, including, but
not limited to, the following indicators:
White Blood Cell Count <310^9/L Neutrophil Count <1.510^9/L <1.510^9/L Hemoglobin <85 <85 g/L Platelet Count <8010^9/L <8010^9/L Serum Creatinine >1.5ULN Total Bilirubin >1.5ULN AST (GOT) >3ULN ALT (GPT) >3ULN Alkaline Phosphatase >2ULN (AST = Aspartate Aminotransferase; GOT = Glutamic-Oxaloacetic Transaminase; ALT = Alanine Aminotransferase; GPT = Glutamic-Pyruvic Transaminase)
- Any contraindications to lumbar puncture.
- Pregnant or breastfeeding women, and patients with plans to conceive during the trial.
- Patients with a known history of allergies to human-derived biological products or those with an allergic predisposition.
- Patients who have undergone hematopoietic stem cell transplantation or lymphatic irradiation before enrollment.
- Patients who have participated in any other clinical trial within the last 3 months.
- Patients with severe comorbidities, including immunodeficiency or coagulation disorders.
- Patients with active suicidal ideation within 6 months before screening or have a history of suicide attempts within 3 years before screening.
- Patients with severe psychiatric symptoms that prevent clinical cooperation.
- Patients with positive for alcohol addiction or drug abuse.
- Patients with malignant tumors.
- Patients who have experienced any of the following events within 12 weeks before enrollment: myocardial infarction, unstable ischemic heart disease, stroke, or New York Heart Association Class IV heart failure.
- Patients with persistent systemic infections and severe local infections.
- Patients unable to undergo magnetic resonance imaging during the trial.
- Patients deemed unsuitable for participation by the investigator.