The Safety and Efficacy of NouvSoma001 in Neuromyelitis Optica Spectrum Disorders

The sample size of this study is not based on statistical hypothesis testing. A total of 69 participants are planned to be enrolled, including 9 participants in the dose-escalation study and 60 participants in the dose-expansion study.

Part 1 will adopt a traditional 3 + 3 dose-escalation design, with a planned enrollment of 9 participants. Participants will be assigned into three cohorts:

Cohort 1: 5 × 10⁹ particles Cohort 2: 1.5 × 10¹⁰ particles Cohort 3: 4.5 × 10¹⁰ particles

If no dose-limiting toxicities (DLTs) are observed within 2 weeks after treatment in the first participant enrolled in Cohort 1, two additional participants may be enrolled. If no DLTs are observed within 2 weeks after treatment in these two additional participants, and at least one of the three participants in the same dose cohort demonstrates a therapeutic response, investigators may make the following decisions based on the preliminary efficacy signals and safety data obtained:

• Continue enrollment in the 5 × 10⁹ particles dose cohort until a total of 6 DLT-evaluable participants are enrolled; or
• Stop further enrollment in the 5 × 10⁹ particles dose cohort and proceed to the next dose level (1.5 × 10¹⁰ particles) for DLT evaluation.

If the first three participants enrolled in Cohort 1 do not experience any DLTs, but none of the participants demonstrate clinical efficacy, and investigators have no additional safety concerns regarding NouvSoma001 extracellular vesicle injection, dose escalation to Cohort 2 (1.5 × 10¹⁰ particles) will be performed for DLT evaluation.

If one participant among the first three participants in Cohort 1 experiences a DLT, enrollment in the 5 × 10⁹ particles dose cohort will continue until a total of 6 DLT-evaluable participants are included.

If two participants among the first three participants in Cohort 1 experience DLTs, investigators may decide, based on the preliminary efficacy and safety data obtained, whether to evaluate a lower dose level (2.5 × 10⁹ particles) for further safety and efficacy assessment.

Cohorts 2 and 3 will follow the same dose-escalation rules as Cohort 1 until completion of Part 1.

In Part 2, the remaining 60 participants will be randomly assigned in a 2:1 ratio to the treatment group and placebo group. The dose level used in Part 2 will be determined based on the results of Part 1.

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 < 3 × 10⁹/L Neutrophil count < 1.5 × 10⁹/L Hemoglobin < 85 g/L Platelet count < 80 × 10⁹/L Serum creatinine > 1.5 × ULN Total bilirubin > 1.5 × ULN Aspartate aminotransferase (AST) > 3 × ULN Alanine aminotransferase (ALT) > 3 × ULN Alkaline phosphatase > 2 × ULN (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.