The Safety and Efficacy of NouvSoma001 in Neuromyelitis Optica Spectrum Disorders

Phase 1RecruitingNCT06620809

Tongji Hospital69 enrolled

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.

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: 1. Continue enrollment in the 5 × 10⁹ particles dose cohort until a total of 6 DLT-evaluable participants are enrolled; or 2. 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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Neuromyelitis Optica Spectrum Disorders

Interventions

Extracellular vesicles derived from human-induced neural stem cells for intrathecal injectionDRUG

Extracellular vesicles derived from human-induced neural stem cells for intrathecal injection

A placebo of extracellular vesicles derived from human-induced neural stem cells for intrathecal injectionDRUG

A placebo of extracellular vesicles derived from human-induced neural stem cells for intrathecal injection

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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 × 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) 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.

Locations (1)

Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology

Wuhan, Hubei, China

RECRUITING