Autologous Activated Adipose-derived Stem Cells (RB-ADSC) Injected Directly Into the Brain for Mild to Moderate Alzheimer's Disease

Study Overview
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Brief Summary
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This is a research study to evaluate the safety of an investigational autologous cell product obtained from participant's own adipose tissue as a possible treatment for Alzheimer disease.

Detailed Description
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This is a Phase 1, Open-Label Safety Study of Escalating Doses of Intracerebroventricular Injections of Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs) in Participants with Mild to Moderate Alzheimer's Disease (AD) whose Treatment is not Addressed Adequately by Available Therapy (i.e., an unmet medical need). The investigational product, which is referred to as RB-ADSC, consists of stem cells obtained from the participant's own adipose tissue by lipoaspirate. After collection, the stem cells are cultured and expanded outside the body, and then reintroduced into the same patient. A soft plastic reservoir (Ommaya reservoir) is implanted under the scalp, communicating with the brain cavities (ventricles). This study will primarily evaluate the safety of RB-ADSC injected in the Ommaya reservoir in a 3 + 3 dose escalation study. The planned enrollment will be 9 participants, 3 participants per escalation Cohort. The primary objectives will evaluate adverse events, serious adverse events, and dose limiting toxicities to determine a recommended phase 2 clinical trial dose. Secondary objectives will evaluate preliminary efficacy measured by clinical assessments, volumetric MRI (Neuro Quant®), CSF biomarkers (Phospho-Tau, Total Tau, AB-42), and diagnostic imaging comparison (Amyloid PET). Each participant will be followed for 12 months after treatment.

Official Title
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Ph 1, Open-Label Safety Study of Escalating Doses of Intracerebroventricular Injections of Ex Vivo Expanded, Autologous ADSCs in Participants With Mild-Moderate AD Whose Treatment is Not Addressed Adequately by Available Therapy

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Biological: RB-ADSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ≥45 and ≤80 years of age Mild to moderate AD diagnosis Adequate cognitive function Non-remarkable clinical laboratory Ability to voluntarily provide written informed consent No tumors or other disease responsible for dementia Well-controlled comorbidities, on stable medications for 3 months The participant is otherwise in good general health The participant must have a relative/caregiver Participant must be able to donate adequate amount of lipoaspirate to establish the final product Caregiver separately meets the specified inclusion/exclusion criteria for caregivers Exclusion Criteria: Taking other medications for AD, except that donepezil memantine, AChEIs including patches, Vitamin E, fish oil, and/or gingko biloba are allowed if doses have been stable for at least 3 months prior to the Screening visit Stem cell implantation of any type within 3 months Existing ventriculoperitoneal shunts Neurological disorders except AD Psychiatric disorders including schizophrenia, bipolar/unipolar depressive disorder, delirium Drug or alcohol abuse or dependence within the past 5 years Participants with a history of cancer in the past 5 years No caregiver available to meet the inclusion criteria for caregivers

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RB-ADSC low dose<br>Participants will receive one dose of 2x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir | Biological: RB-ADSC<br>* Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs)<br>|
| Experimental: RB-ADSC medium dose<br>Participants will receive one dose of 5x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir | Biological: RB-ADSC<br>* Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs)<br>|
| Experimental: RB-ADSC high dose<br>Participants will receive one dose of 10x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir | Biological: RB-ADSC<br>* Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of RB-ADSC treatment in study participants with AD | Safety will be determined by incidence, type and severity of adverse events (AE) and serious adverse events (SAE) graded according to CTCAE v5.0 and CRS revised grading system and defined by clinical relevant findings at every visit and week 28 post-treatment in physical examination, vital signs and laboratory data | up to 28 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) | Measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) is a cognitive performance test. The ADAS-cog score ranges from 0 to 70, with higher scores indicating greater cognitive impairment (lower score is worse outcome). | up to 52 weeks | 
| Change from Baseline in Mini Mental State Examination (MMSE) | Measured by the Mini Mental State Examination (MMSE). MMSE is a performance-based test of global cognitive status.. The MMSE score ranges from 0 to 30, with lower scores indicating greater cognitive impairment (lower score is worse outcome). | up to 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's Disease, AD, Autologous, Stem cells