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This is a Phase 1b Extension Trial to allow repeat intracerebroventricular injections of RB-ADSCs in subjects previously treated in and successfully completed RBI Protocol RB-ADSC-02. In the previous Phase 1 clinical trial, RB-ADSC-02, subjects with mild to moderate Alzheimer's disease (AD) received a single intraventricular injection of RB-ADSC. RB-ADSC will be delivered intracerebroventricularly every 2 months via the previously implanted Ommaya reservoir for up to 6 injections in total. The primary objective of safety is performed 2 months after the last dose administration at the month 12 follow-up visit. The secondary objective endpoint evaluations of efficacy are performed at the month 6 and 12 visits.
This is a Phase 1b Extension Trial to allow repeat intracerebroventricular injections of RB-ADSCs in subjects previously treated in and successfully completed RBI Protocol RB-ADSC-02. In the previous Phase 1 clinical trial, RB-ADSC-02, subjects with mild to moderate Alzheimer's disease (AD) received a single intraventricular injection of RB-ADSC.
RB-ADSC will be delivered intracerebroventricularly every 2 months via the previously implanted Ommaya reservoir for up to 6 injections in total. Participants will be followed for 2 months after the last administration. The primary objective is safety and tolerability of repeated dosing of RB-ADSC. Adverse events (AEs) and serious adverse events (SAEs) will be assessed by the incidence and severity of dose-limiting toxicity (DLT) and other AEs, incidence and severity of cytokine response syndrome, vital sign measurements, clinical laboratory tests and physical examination. Preliminary efficacy of repeated dosing will be evaluated with clinical assessments (MMSE, FAST, ADAS-Cog), volumetric MRI (NeuroQuant), CSF biomarkers (phosphor-Tau, total-Tau,AB-42), and diagnostic imaging comparison (Amyloid-PET).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| RB-ADSC low dose | Experimental | Participants will receive 2x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir every 2 months for up to a total of 6 doses |
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| RB-ADSC medium dose | Experimental | Participants will receive 5x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir every 2 months for up to a total of 6 doses |
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| RB-ADSC high dose | Experimental | Participants will receive 10x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir every 2 months for up to a total of 6 doses |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| RB-ADSC | Biological | Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs) |
|
| Measure | Description | Time Frame |
|---|---|---|
| The safety of repeated 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 2 month following last dose in physical examination, vital signs and laboratory data | up to 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| Change from Baseline in cerebrospinal fluid (CSF) biomarker pTau | CSF Biomarkers will be measured with the ADmark® phospho-tau/total-tau/ Abeta-42 assay to determine the levels of Phosphorylated-Tau protein in the cerebrospinal fluid (CSF). | Baseline, Month 6, Month 12 |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker Total-Tau |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Robert Lynn | Contact | 877-240-1660 | robert@regenerationbiomedical.com |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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CSF Biomarkers will be measured with the ADmark® phospho-tau/total-tau/ Abeta-42 assay to determine the levels of Total-Tau protein in the cerebrospinal fluid (CSF). |
| Baseline, Month 6, Month 12 |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker Ab42 | CSF Biomarkers will be measured with the ADmark® phospho-tau/total-tau/ Abeta-42 assay to determine the levels of Ab42 in the cerebrospinal fluid (CSF). | Baseline, Month 6, Month 12 |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker ratios reported as amyloid-tau index (ATI) | CSF Biomarkers will be measured with the ADmark® phospho-tau/total-tau/ Abeta-42 assay to determine the levels of Phosphorylated-Tau protein, Total-Tau protein, and Ab42 in the cerebrospinal fluid (CSF) to calculate ratios and report the amyloid-tau index (ATI). | Baseline, Month 6, Month 12 |
| Change from Baseline in Amyloid Positron Emission Tomography (Amyloid-PET) | Amyloid-PET will be used to quantitatively assess amyloid plaque deposition in the brain | Baseline, Month 6, Month 12 |
| Change from Baseline in MMSE | Cognitive function will be evaluated with the Mini Mental State Examination (MMSE). The range for the total MMSE score is 0 to 30, with lower scores indicating greater level of impairment. | Baseline, Month 6, Month 12 |
| Change from Baseline in ADAS-cog13 | Cognitive function will be assessed using the AD Assessment Scale - Cognitive (ADAS-cog13). The ADAS-Cog13 scale ranges from 0 to 85, with higher scores indicating greater disease severity. | Baseline, Month 6, Month 12 |
| Change from Baseline in FAST | Functional abilities will be assessed using the Functional Assessment Staging Tool (FAST). The tool consists of seven stages, with higher scores indicating more severe impairment. | Baseline, Month 6, Month 12 |
| Change from Baseline in MoCA | Mild cognitive impairment and the early onset of dementia will be assessed using the Montreal Cognitive Assessment (MoCA) | Baseline, Month 6, Month 12 |
| Change from Baseline in Volumetric MRI with Contrast | Volumetric MRI with contrast of the brain will be used to detect and monitor brain abnormalities. | Baseline, Month 6 and Month 12 |
| Change from Baseline in NeuroQuant MRI | NeuroQuant MRI will be used to measure volumes of brain structures. | Baseline, Month 6 and Month 12 |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |