Mild to Moderate Alzheimer's Disease
Conditions
Keywords
Exosomes
Brief summary
This study is divided into two phases: a dose-escalation phase and an expansion cohort phase. The dose-escalation phase is a single-center study, while the expansion cohort phase is a multicenter, prospective, randomized, double-blind, placebo-controlled study.
Detailed description
Dose-Escalation Phase: A traditional "3+3" dose-escalation design will be used. Subjects will be sequentially assigned to one of three dose groups (0.75 × 10¹⁰ Particles/mL, 1.50 × 10¹⁰ Particles/mL, 3.00 × 10¹⁰ Particles/mL; 1 mL per nostril, total dose volume of 2 mL per administration, twice weekly with an interval of 3±1 days between doses, for 12 weeks). Three subjects will be enrolled in each dose group. Escalation to the next dose level will proceed if no Dose-Limiting Toxicity (DLT) is observed in these 3 subjects. If 1 out of 3 subjects experiences a DLT, an additional 3 subjects will be enrolled in the same dose group. Escalation to the next dose level will proceed if no DLT is observed in these additional 3 subjects. Expansion Cohort Phase: 24 subjects will be randomized in a 1:1 ratio to either the experimental group (exosome group) or the control group (exosome mimetic group). The dose for the experimental group in this phase will be determined by the Safety Review Committee based on the safety and efficacy data from the dose-escalation phase. The dosing frequency and duration will be 1 mL per nostril, total dose volume of 2 mL per administration, twice weekly with an interval of 3±1 days between doses, for 12 weeks.
Interventions
DRUGExosomes derived from umbilical cord mesenchymal stem cell for intranasal drop
Specification: 2.0 mL/vial. Particle concentration: (Low) 0.75 × 10¹⁰ Particles/mL, (Medium) 1.50 × 10¹⁰ Particles/mL, (High) 3.00 × 10¹⁰ Particles/mL.
DRUGA placebo of exosomes derived from umbilical cord mesenchymal stem cell for intranasal drop
Specification: 2.0 mL/vial.
Sponsors
Xuanwu Hospital, Beijing
Carrier Biomed (Suzhou) Co., Ltd
Institute of Process Engineering, Chinese Academy of Sciences
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 50 years, male or female. * Clinical diagnosis of AD (mild to moderate stage, corresponding to clinical stage 4-5 at screening according to the 2024 National Institute on Aging/Alzheimer's Association \[NIA/AA\] criteria). * Patients with cerebrospinal fluid biomarker data supporting an AD diagnosis within the past 3 years, or a positive amyloid Positron Emission Tomography (PET) scan result within the past 3 years, or a plasma p-tau217 test result indicating brain amyloid positivity. * Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) scan performed within 6 months prior to screening shows findings consistent with the clinical diagnosis of mild to moderate AD and no other clinically significant comorbid pathologies, particularly cerebrovascular disease. If an MRI or CT scan is not available within the 6 months prior to screening, an MRI must be completed and results confirmed before the subject initiates treatment. * Modified Hachinski Ischemic Score (mHIS) ≤ 4. * Mini-Mental Status Examination (MMSE) score between 10 and 24 (inclusive). * The subject has a clearly identified and reliable caregiver who meets the following criteria: able to independently read and understand relevant study documents at the study site and communicate necessary information with the investigator; willing to comply with clinical study procedures and ensure the provision of accurate information regarding the subject's status throughout the study; resides with the subject or provides care for the subject for no less than 2 hours per day on at least 3 days per week. * Female subjects of childbearing potential (including women of reproductive age and those less than 1 year postmenopausal) must use effective contraceptive methods throughout the study. * Patients have been on stable doses of cholinesterase inhibitors (e.g., donepezil, rivastigmine, galantamine, huperzine A), excitatory amino acid receptor antagonists (e.g., memantine), or other cognitive-enhancing medications (e.g., sodium oligomannate) for at least 60 days prior to enrollment and must continue on the same doses throughout the study period. * The subject or their legal guardian voluntarily signs a written informed consent form and is able to comply with the study requirements for dosing and follow-up.
Exclusion criteria
* Patients with a known allergic reaction to the investigational drug or similar drugs. * Patients with a known allergic constitution. * Previous receipt of umbilical cord mesenchymal stem cell therapy. * Laboratory findings (any of the following): absolute neutrophil count \< 1.0 × 10⁹/L, platelet count \< 100 × 10⁹/L, serum creatinine \> upper limit of normal range, serum total bilirubin, alanine aminotransferase, or aspartate aminotransferase \> 2 × upper limit of normal range. * Contraindications for MRI, including but not limited to: presence of cardiac pacemaker, defibrillator, cardiac stent, artificial heart valve, post-aneurysm surgery metal clips, implanted drug infusion device, any implanted electronic device (nerve stimulator, bone growth stimulator), intravascular embolization coils, filters, ECG monitor, metal sutures, shrapnel or buckshot, fracture fixation hardware, cochlear implant, middle ear implant, intraocular metallic foreign body, etc. * Subject has Parkinson's disease, multiple cerebral infarction, vascular dementia, Huntington's disease, hydrocephalus, progressive supranuclear palsy, multiple sclerosis, epilepsy, intellectual disability, or a history of significant traumatic brain injury (with or without persistent neurological deficits) or known structural brain abnormalities. * Serious systemic infection within 3 months prior to the screening period. * Positive for Hepatitis B surface antigen, e antigen, or e antibody, or positive for Hepatitis B core antibody with detectable Hepatitis B virus DNA; positive for Hepatitis C virus antibody; positive for syphilis serology; or positive for Human Immunodeficiency Virus antibody. * History of alcohol abuse, drug abuse, or psychiatric illness within 10 years prior to screening. * History of malignant tumors. * Uncontrolled or poorly controlled cardiovascular, cerebrovascular, hepatic, renal, pulmonary, endocrine or other systemic diseases. * Presence of severe aphasia, auditory/visual impairment, unstable cardiac arrhythmia, or other severe conditions that would preclude completion of cognitive assessments or receipt of treatment. * Any other severe, advanced, or end-stage disease with a life expectancy of less than 12 months. * Known pregnancy or breastfeeding, or positive pregnancy test prior to randomization. * Current participation in another interventional clinical study that may interfere with outcome assessments. * Any other condition deemed by the investigator to make the subject unsuitable for participation or that may pose a significant risk to the patient.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of serious adverse events | 24 weeks (±1 week) | The proportion of patients who experienced severe adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Alzheimer's Disease Assessment Scale-cog | 24 weeks (±1 week） | Change from baseline in the Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog) score |
| Incidence of adverse events | 24 weeks (±1 week) | The proportion of patients who experienced adverse events. |
| Incidence of severe adverse events | 12 weeks (±1 week) | The proportion of patients who experienced severe adverse events. |
| Alzheimer's disease assessment scale-cognitive section（ADAS-cog） | 12 weeks (±1 week) | Change from baseline in ADAS-cog score |
| Mini-Mental State Examination (MMSE) | 24 weeks (±1 week) | Change from baseline in Mini-Mental State Examination (MMSE) score |
| Montreal Cognitive Assessment (MoCA) | 24 weeks (±1 week) | Change from baseline in Montreal Cognitive Assessment (MoCA) score |
| Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) | 24 weeks (±1 week) | Change from baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) score |
| Neuropsychiatric Inventory (NPI) | 24 weeks (±1 week) | Change from baseline in Neuropsychiatric Inventory (NPI) score |
Countries
China
Contacts
CONTACTJunwei Hao, MD; PhD
CONTACTGaoting Ma, MD
PRINCIPAL_INVESTIGATORJunwei Hao, MD; PhD
Xuanwu Hospital, Beijing
Outcome results
None listed