hUC-MSC-sEV-001 Nasal Drops for Neurodegenerative Diseases

Official title

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

Overview

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.

Interventions

• Drug hUC-MSC-sEV-001 nasal drops
  hUC-MSC-sEV-001 nasal drops

Primary outcome measures

• Alzheimer's disease: Change in Alzheimer's disease assessment scale-cognitive section（ADAS-cog） [Time frame: 12 months]
• Parkinson's disease: Change in MDS Unified-Parkinson Disease Rating Scale(MDS-UPDRS) [Time frame: 12 months]
• multiple system atrophy: Unified Multiple System Atrophy Rating Scale（Part I and Part II） [Time frame: 12 months]
• lewy body dementia: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) [Time frame: 12 months]
• frontotemporal dementia: CDR Dementia Staging Instrument PLUS National Alzheimer's Coordinating Center Behavior and Language Domains（CDR+NACC FTLD） [Time frame: 12 months]
• Amyotrophic lateral sclerosis: Change in Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) [Time frame: 6 months]

Secondary outcome measures (12)

• Barthel index [Time frame: 6 months, 12months]
• mini mental status exam(MMSE) [Time frame: 6 months, 12months]
• EQ-5D-5L [Time frame: 6 months, 12months]
• Alzheimer's disease: sum of boxes of the CDR（CDR-SB） [Time frame: 6 months, 12months]
• Alzheimer's disease: Alzheimer's Disease Cooperative Study - Activities of Daily Living （ADCS-ADL） [Time frame: 6 months, 12months]
• multiple system atrophy: Composite Autonomic Symptom Score [Time frame: 6 months, 12months]
• Clinical Global Impression [Time frame: 6 months, 12months]
• lewy body dementia: MDS-UPRDS [Time frame: 6 months, 12months]
• Lewy body dementia：Neuropsychiatric Inventory（NPI） [Time frame: 6 months, 12months]
• frontotemporal dementia: NPI [Time frame: 6 months, 12months]
• frontotemporal dementia: ADAS-cog [Time frame: 6 months, 12months]
• Amyotrophic lateral sclerosis: Change in forced vital capacity to predicted value ratio (FVC% pred) [Time frame: 6 months]

Eligibility criteria

General Criteria:

Inclusion criteria

• 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.

Exclusion criteria

• 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 ≤ 1.0.
• 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 ≤ 3.
• Stable treatment regimen for at least 1 month prior to dosing.

Exclusion criteria

1\. 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 ≥ 14.
• 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 ≤ 1.0.
• 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.
• Clinical Dementia Rating (CDR) score ≤ 1.0.
• Stable treatment regimen for at least 1 month prior to dosing.

Exclusion criteria

1\. Diagnosis of severe central nervous system diseases other than FTD that may be the cause of the patient's FTD symptoms or may affect the study objectives.

Amyotrophic Lateral Sclerosis (ALS) Specific Criteria:

Inclusion criteria

• Diagnosis of Amyotrophic Lateral Sclerosis (ALS) meeting the diagnostic criteria (Revised El Escorial Criteria, 2000 or Airlie House Criteria) at the level of definite, probable, or laboratory-supported probable ALS.
• Disease duration ≥ 6 months and ≤ 2 years (from the first occurrence of any ALS symptom).
• Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) score: each individual item score ≥ 2 points (with the three respiratory items - Dyspnea, Orthopnea, and Respiratory Insufficiency - all scoring 4 points).
• Stable treatment regimen for at least 1 month prior to dosing.

Exclusion criteria

1\. Diagnosis of non-ALS patients based on clinical presentation and available auxiliary clinical examinations (neurophysiology, MRI or other imaging techniques, laboratory tests, etc.).

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

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Xuanwu Hospital, Capital Medical University — Beijing

Identifiers

NCT: NCT06607900 · XMEC-2024-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗