Clinical trial NCT06620809: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Neuromyelitis Optica Spectrum Disorders
Keywords: Neuromyelitis Optica Spectrum Disorders
extracelluar vesicles
Lead sponsor: Tongji Hospital
Sponsor class: OTHER
Collaborators: name: iRegene Therapeutics Co., Ltd.
First posted: 2024-10-01
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

Eligibility criteria: 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 \&lt;3\*10\^9/L Neutrophil Count \&lt;1.5\*10\^9/L \&lt;1.5\*10\^9/L Hemoglobin \&lt;85 \&lt;85 g/L Platelet Count \&lt;80\*10\^9/L \&lt;80\*10\^9/L Serum Creatinine \&gt;1.5\*ULN Total Bilirubin \&gt;1.5\*ULN AST (GOT) \&gt;3\*ULN ALT (GPT) \&gt;3\*ULN Alkaline Phosphatase \&gt;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.

Primary outcomes:
measure: The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
timeFrame: Up to 6 month after treatment initiation
Secondary outcomes:
measure: The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
timeFrame: Up to 18 month after treatment initiation
measure: Magnetic Resonance Imaging（MRI）scan of the brain and spinal cord at month 3、6
timeFrame: Up to 6 month after treatment initiation
measure: The score of Visual analogue scale（VAS） at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: Brief Pain Inventory - Short form (BPI-SF) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Expanded Disability Status Scale （EDSS） at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Fecal Incontinence Severity Index (FISI) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hauser Ambulance Index （contains The timed 25-foot walk）at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hamilton Despression Scale at month 1、3、6 compared with baseline and control group
timeFrame: Up to 6 month after treatment initiation
measure: The score of Hamilton Anxiety Scale at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The Modified Rankin Scale (mRS)
timeFrame: Up to 6 month after treatment initiation
measure: The value of Quality of Life (EQ-5D-5L) at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) events at month 1、3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of Nfl、GFAP in the serum at month 1、3、6 compared with baseline and control group
timeFrame: Up to 6 month after treatment initiation
measure: The value of white blood cell count in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of QAlb in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of Nfl in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of GFAP in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of IL-1β in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of IL-6 in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of TNF-α in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: The value of sTREM2 in cerebrospinal fluid at month 3、6 compared with baseline and control group.
timeFrame: Up to 6 month after treatment initiation
measure: Examination of visual function at month 1、3、6
timeFrame: Up to 6 month after treatment initiation
measure: Optical coherence tomography (OCT) at month 3、6
timeFrame: Up to 6 month after treatment initiation
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
Study officials:
affiliation: Tongji Hospoital
name: Dai-shi Tian, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Hospoital
name: Wei Wang, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tongji Hospital
name: Chuan Qin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.