An Open-Label Exploratory Clinical Trial to Assess the Safety and Efficacy of NouvSoma001 in the Treatment of Neuromyelitis Optica Spectrum Disorders
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 69
- 试验地点
- 1
- 主要终点
- The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤
- •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.
排除标准
- •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.
研究组 & 干预措施
Extracellular vesicles group
Patients in this group will receive extracellular vesicles derived from human-induced neural stem cells for intrathecal injection once a day for 1 day.
干预措施: Extracellular vesicles derived from human-induced neural stem cells for intrathecal injection (Drug)
Extracellular vesicles placebo group
Patients in this group will receive a placebo of extracellular vesicles derived from human-induced neural stem cells for intrathecal injection once a day for 1 day.
干预措施: A placebo of extracellular vesicles derived from human-induced neural stem cells for intrathecal injection (Drug)
结局指标
主要结局
The incidence and severity of all adverse events (AE) and serious adverse events (SAE)
时间窗: Up to 6 month after treatment initiation
The assessment of adverse events and serious adverse events
次要结局
- The Modified Rankin Scale (mRS)(Up to 6 month after treatment initiation)
- Magnetic Resonance Imaging (MRI) scans of the brain and spinal cord at month 1 and month 6(Up to 6 month after treatment initiation)
- The score of Visual analogue scale（VAS）(Up to 6 month after treatment initiation)
- Brief Pain Inventory - Short form (BPI-SF)(Up to 6 month after treatment initiation)
- The score of Expanded Disability Status Scale （EDSS）(Up to 6 month after treatment initiation)
- The score of Fecal Incontinence Severity Index (FISI)(Up to 6 month after treatment initiation)
- The score of Hauser Ambulance Index （contains The timed 25-foot walk）(Up to 6 month after treatment initiation)
- The score of Hamilton Anxiety Rating Scale(Up to 6 month after treatment initiation)
- The score of Hamilton Depression Rating Scale(Up to 6 month after treatment initiation)
- The value of Quality of Life (EQ-5D-5L)(Up to 6 month after treatment initiation)
- The incidence of Columbia-Suicide Severity Rating Scale (C-SSRS) events(Up to 6 month after treatment initiation)
- The value of white blood cell count in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of QAlb in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of Nfl in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of GFAP in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of IL-1β in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of IL-6 in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of TNF-α in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- The value of sTREM2 in cerebrospinal fluid at month 1、6 compared with baseline and control group.(Up to 6 month after treatment initiation)
- Examination of visual function(Up to 6 month after treatment initiation)
- Optical coherence tomography (OCT)(Up to 6 month after treatment initiation)
- Translocator Protein (TSPO) PET imaging at month 1(Up to 1 month after treatment initiation)
- Chest computed tomography (CT) scans at month 6 and month 18(Up to 18 month after treatment initiation)
- Tumor marker assessment at month 6(Up to 6 month after treatment initiation)
- The incidence and severity of all adverse events (AE) and serious adverse events (SAE)(Up to 18 month after treatment initiation)
- The value of Nfl、GFAP in the serum at month 1、3、6 compared with baseline and control group(Up to 6 month after treatment initiation)