The Safety and Efficacy of NouvSoma001 in Neuromyelitis Optica Spectrum Disorders

Official title

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

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.

Detailed 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.

Interventions

• Drug Extracellular vesicles derived from human-induced neural stem cells for intrathecal injection
  Extracellular vesicles derived from human-induced neural stem cells for intrathecal injection（5×10\^9 particles）
• Drug A placebo of extracellular vesicles derived from human-induced neural stem cells for intrathecal injection
  Extracellular vesicles placebo(5×10\^9 particles）

Primary outcome measures

• The incidence and severity of all adverse events (AE) and serious adverse events (SAE) [Time frame: Up to 6 month after treatment initiation]

Secondary outcome measures (12)

• The incidence and severity of all adverse events (AE) and serious adverse events (SAE) [Time frame: Up to 18 month after treatment initiation]
• Magnetic Resonance Imaging（MRI）scan of the brain and spinal cord at month 3、6 [Time frame: Up to 6 month after treatment initiation]
• The score of Visual analogue scale（VAS） at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• Brief Pain Inventory - Short form (BPI-SF) at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The score of Expanded Disability Status Scale （EDSS） at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The score of Fecal Incontinence Severity Index (FISI) at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The score of Hauser Ambulance Index （contains The timed 25-foot walk）at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The score of Hamilton Despression Scale at month 1、3、6 compared with baseline and control group [Time frame: Up to 6 month after treatment initiation]
• The score of Hamilton Anxiety Scale at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The Modified Rankin Scale (mRS) [Time frame: Up to 6 month after treatment initiation]
• The value of Quality of Life (EQ-5D-5L) at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]
• The incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) events at month 1、3、6 compared with baseline and control group. [Time frame: Up to 6 month after treatment initiation]

Eligibility criteria

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\*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)

• 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.

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

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and — Wuhan

Publications

• Dulamea AO, Sirbu-Boeti MP, Bleotu C, Dragu D, Moldovan L, Lupescu I, Comi G. Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica. Neural Regen Res. 2015 Nov;10(11):1841-5. doi: 10.4103/1673-5374.165325. PMID 26807122
• Xu H, Jiang W, Li X, Jiang J, Afridi SK, Deng L, Li R, Luo E, Zhang Z, Huang YA, Cui Y, So KF, Chen H, Qiu W, Tang C. hUC-MSCs-derived MFGE8 ameliorates locomotor dysfunction via inhibition of ITGB3/ NF-kappaB signaling in an NMO mouse model. NPJ Regen Med. 2024 Jan 20;9(1):4. doi: 10.1038/s41536-024-00349-z. PMID 38242900

Identifiers

NCT: NCT06620809 · NouvSoma001inNMOSD

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗