The Safety and Efficacy of NouvSoma001 in Neuromyelitis Optica Spectrum Disorders

An Open-Label Exploratory Clinical Trial to Assess the Safety and Efficacy of NouvSoma001 in the Treatment of Neuromyelitis Optica Spectrum Disorders

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.

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.

Inclusion Criteria:

1. Patients must meet the 2015 International Consensus Diagnostic Criteria for Neuromyelitis Optica Spectrum Disorder (NMOSD) and test positive for AQP4 antibodies.
2. Symptom onset occurred within 7 days prior to enrollment, with associated severe pain, lower limb motor dysfunction, or urinary/bowel impairment.
3. Males or Females aged between 18 and 65 years.
4. The Expanded Disability Status Scale (EDSS) score prior to the current disease episode is ≤ 4.
5. Female participants of childbearing potential must present a negative pregnancy test at screening and agree to use effective contraception throughout the study period.
6. Informed consent must be obtained from the patient or their legal representative, with a signed consent form must be provided.

Exclusion Criteria:

1. Abnormal laboratory indicators of the subjects need to be excluded, including, but not limited to, the following indicators:

   White Blood Cell Count <3*10^9/L Neutrophil Count <1.5*10^9/L <1.5*10^9/L Hemoglobin <85 <85 g/L Platelet Count <80*10^9/L <80*10^9/L Serum Creatinine >1.5*ULN Total Bilirubin >1.5*ULN AST (GOT) >3*ULN ALT (GPT) >3*ULN Alkaline Phosphatase >2*ULN (AST = Aspartate Aminotransferase; GOT = Glutamic-Oxaloacetic Transaminase; ALT = Alanine Aminotransferase; GPT = Glutamic-Pyruvic Transaminase)

2. Any contraindications to lumbar puncture.

3. Pregnant or breastfeeding women, and patients with plans to conceive during the trial.

4. Patients with a known history of allergies to human-derived biological products or those with an allergic predisposition.

5. Patients who have undergone hematopoietic stem cell transplantation or lymphatic irradiation before enrollment.

6. Patients who have participated in any other clinical trial within the last 3 months.

7. Patients with severe comorbidities, including immunodeficiency or coagulation disorders.

8. Patients with active suicidal ideation within 6 months before screening or have a history of suicide attempts within 3 years before screening.

9. Patients with severe psychiatric symptoms that prevent clinical cooperation.

10. Patients with positive for alcohol addiction or drug abuse.

11. Patients with malignant tumors.

12. 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.

13. Patients with persistent systemic infections and severe local infections.

14. Patients unable to undergo magnetic resonance imaging during the trial.

15. Patients deemed unsuitable for participation by the investigator.