A Multi-center, Open, Single-arm, Basket-design Clinical Trial to Evaluate the Safety and Efficacy of Human Umbilical Cord Mesenchymal Stem Cell-derived Small Extracellular Vesicles hUC-MSC-sEV-001 Nasal Drops for the Treatment of Multiple Neurodegenerative Diseases
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 120
- 试验地点
- 1
- 主要终点
- Alzheimer's disease: Change in Alzheimer's disease assessment scale-cognitive section（ADAS-cog）
研究概览
简要总结
To evaluate the safety and preliminary efficacy of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles hUC-MSC-sEV-001 nasal drops in multiple neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, multiple system atrophy, Lewy body dementia, frontotemporal dementia, and amyotrophic lateral sclerosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-80 years (inclusive), any gender.
- •Subjects or their legal guardians voluntarily sign a written informed consent form and are able to comply with the study requirements for dosing and follow-up.
排除标准
- •Subjects who have received allogeneic mesenchymal progenitor cell therapy or its derived small extracellular vesicles.
- •Subjects with abnormal nasal anatomy, nasal damage, severe rhinitis, or other nasal conditions that may affect the administration of the investigational product.
- •Subjects requiring nasogastric tube insertion.
- •Suffering from other uncontrolled diseases that may interfere with the study results, including but not limited to severe local infection, systemic infection, or immunodeficiency.
- •Combined with malignant tumors, hematological malignancies, or other serious systemic diseases.
- •Clinically significant history of allergic reactions, especially drug allergic reactions.
- •Severe renal insufficiency: creatinine clearance (CrCl) < 30 mL/min (calculated by Cockcroft-Gault formula), or other known severe renal diseases.
- •Peripheral blood hemoglobin (HGB) < 100 g/L, absolute neutrophil count (NEUT) < 1.5 × 10⁹/L, platelet count (PLT) < 100 × 10⁹/L, white blood cell count (WBC) < 4.0 × 10⁹/L or ≥ 12 × 10⁹/L, serum albumin < 30 g/L; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≥ 3 × upper limit of normal (ULN).
- •HBsAg positive, or HBcAb positive with HBV DNA positive, hepatitis C virus (HCV) antibody positive, peripheral blood HCV RNA positive, HIV antibody positive; CMV DNA positive, syphilis serology positive.
- •Contraindications to MRI examination (e.g., metal implants) or inability to tolerate MRI (e.g., claustrophobia).
- •Women of childbearing potential not intending to use effective contraception during the trial or within 90 days after the last dose and with a positive pregnancy test record; pregnant or lactating women; men who are sexually active during the trial or within 90 days after the last dose and not intending to use effective contraception; or men planning to donate sperm during the trial or within 90 days after the last dose.
- •Vaccination within 1 month prior to the first dose or planned during the period from enrollment until the end of follow-up.
- •Participation in other clinical drug studies within the past 30 days.
- •Any condition that, in the investigator's judgment, may compromise the subject's ability to understand and/or comply with the study procedures and/or follow-up.
- •Alzheimer's Disease (AD) Specific Criteria:
- •Inclusion Criteria:
- •Probable AD as defined by the 2011 National Institute on Aging-Alzheimer's Association (NIA-AA) criteria.
- •Clinical Dementia Rating (CDR) score ≤ 1.
- •Subjects have an identified, reliable caregiver.
- •Stable treatment regimen for at least 1 month prior to dosing.
- •Exclusion Criteria:
- •Major history of significant brain injury with persistent neurological impairment (with or without) or known structural brain abnormalities.
- •Cognitive impairment due to other causes: central nervous system infection, Creutzfeldt-Jakob disease, traumatic dementia, other physical/chemical factors (e.g., drug intoxication, alcoholism, carbon monoxide poisoning), major systemic illnesses (e.g., hepatic encephalopathy, pulmonary encephalopathy), intracranial space-occupying lesions (e.g., subdural hematoma, brain tumor), endocrine disorders (e.g., thyroid disease, parathyroid disease), vitamin B12 or folate deficiency, or any other known causes.
- •Parkinson's Disease (PD) Specific Criteria:
- •Inclusion Criteria:
- •Diagnosis of PD according to the 2015 Movement Disorder Society (MDS) clinical diagnostic criteria for PD.
- •Hoehn and Yahr stage ≤
- •Stable treatment regimen for at least 1 month prior to dosing.
- •Exclusion Criteria:
- •Parkinsonism other than PD, including but not limited to progressive supranuclear palsy (PSP), multiple system atrophy (MSA), vascular parkinsonism, drug-induced parkinsonism, essential tremor, primary dystonia.
- •Multiple System Atrophy (MSA) Specific Criteria:
- •Inclusion Criteria:
- •Diagnosis of possible or probable multiple system atrophy.
- •Time since diagnosis < 3 years from baseline, with an expected survival of at least 3 years.
- •Stable treatment regimen for at least 1 month prior to dosing.
- •Exclusion Criteria:
- •Modified Unified Multiple System Atrophy Rating Scale (UMSARS) Part I score ≥
- •Presence of any condition that, in the investigators' judgment, affects the diagnosis or assessment of MSA.
- •Dementia with Lewy Bodies (DLB) Specific Criteria:
- •Inclusion Criteria:
- •Meets the revised consensus criteria for DLB (Fourth Consensus Report of the DLB Consortium, 2017).
- •Severity of motor symptoms must be ≤ stage 3 on the Hoehn and Yahr scale.
- •Clinical Dementia Rating (CDR) score ≤ 1.
- •Stable treatment regimen for at least 1 month prior to dosing.
- •Exclusion Criteria:
- •Patients currently diagnosed with any primary psychiatric disorder (e.g., schizophrenia, bipolar disorder, or major depressive episode) according to DSM-V.
- •Patients with clinically significant or unstable systemic illness and exposure to toxicants within the past 5 years.
- •Frontotemporal Dementia (FTD) Specific Criteria:
- •Inclusion Criteria:
- •Meets the 2017 International Research Society (IRS) diagnostic criteria for FTD.
- 另有 12 项未显示
研究组 & 干预措施
hUC-MSC-sEV-001 group
hUC-MSC-sEV-001 nasal drops treatment
干预措施: hUC-MSC-sEV-001 nasal drops (Drug)
结局指标
主要结局
Alzheimer's disease: Change in Alzheimer's disease assessment scale-cognitive section（ADAS-cog）
时间窗: 12 months
ADAS-Cog is comprised of 11 modalities that evaluate memory, praxis, and language deficiencies. The total score range is 0 to 70 points, with higher scores indicating greater cognitive impairment.
Parkinson's disease: Change in MDS Unified-Parkinson Disease Rating Scale(MDS-UPDRS)
时间窗: 12 months
The MDS-UPDRS is defined by 4 Parts, each composed by a different number of items. The MDS-UPDRS has a minimum score of 0 and a maximum score of 260. The higher the score, the more severe the impairment.
multiple system atrophy: Unified Multiple System Atrophy Rating Scale（Part I and Part II）
时间窗: 12 months
UMSARS is a clinical tool designed to assess the severity and progression of MSA. The scale is divided into multiple parts, with Part I focusing on functional disability based on the history and self-report symptoms and Part II the severity of motor symptoms through a physical examination. The higher score, the severer impairment.
lewy body dementia: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)
时间窗: 12 months
ADCS-CGIC provides a clinician-rated, subjective evaluation of a patient\&#39;s cognitive, behavioral, and functional performance based on interviews and observations. The scoring typically uses a 7-point scale. The lower score, the better changes in overall condition.
frontotemporal dementia: CDR Dementia Staging Instrument PLUS National Alzheimer's Coordinating Center Behavior and Language Domains（CDR+NACC FTLD）
时间窗: 12 months
The CDR Dementia Staging Instrument provides a global assessment of cognitive and functional decline, while the NACC Behavior and Language Domains offer a more nuanced view of neuropsychiatric symptoms and language impairments.
Amyotrophic lateral sclerosis: Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
时间窗: 6 months
The ALSFRS-R is rating scale (ratings 0 = can't do, to 4 = normal ability) used to determine participants' assessment of their capability and independence in 12 functional activities. This is a validated scale, both in person and by phone, which provides a total score from four sub-scores which assess speech and swallowing (bulbar function), use of upper extremities (cervical function), gait and turning in bed (lumbar function), and breathing (respiratory function). Total scores range from 0 (most impaired) to 48 (normal ability).
次要结局
- Barthel index(6 months, 12months)
- mini mental status exam(MMSE)(6 months, 12months)
- EQ-5D-5L(6 months, 12months)
- Alzheimer's disease: sum of boxes of the CDR（CDR-SB）(6 months, 12months)
- Alzheimer's disease: Alzheimer's Disease Cooperative Study - Activities of Daily Living （ADCS-ADL）(6 months, 12months)
- multiple system atrophy: Composite Autonomic Symptom Score(6 months, 12months)
- Clinical Global Impression(6 months, 12months)
- lewy body dementia: MDS-UPRDS(6 months, 12months)
- Lewy body dementia：Neuropsychiatric Inventory（NPI）(6 months, 12months)
- frontotemporal dementia: NPI(6 months, 12months)
- frontotemporal dementia: ADAS-cog(6 months, 12months)
- Amyotrophic lateral sclerosis: Change in forced vital capacity to predicted value ratio (FVC% pred)(6 months)
- Amyotrophic lateral sclerosis: Change in the Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40).(6 months)
- Amyotrophic lateral sclerosis: Change in the Edinburgh Cognitive and Behavioral ALS Screen (ECAS).(6 months)
- Amyotrophic lateral sclerosis: Change in the Neurophysiological Index (NI) and Compound Muscle Action Potential (CMAP) score.(6 months)
- Amyotrophic lateral sclersis: Change in the Rasch Overall ALS Disability Scale (ROADS).(6 months)
- Adverse effects(3months, 6 months, 12months)