Alzheimer Disease
Conditions
Keywords
AD, Autologous, Stem cells, Cell therapy, Alzheimer Disease, RB-ADSC
Brief summary
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.
Detailed description
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).
Interventions
BIOLOGICALRB-ADSC
Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (ADSCs)
Sponsors
Regeneration Biomedical, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Successful completion of the Phase 1 single dose administration study of RB-ADSC, Protocol RB-ADSC-02. 2. Written informed consent to participate in this Phase 1b Extension Study either provided by the participant or a legal representative 3. The participant must have a relative/caregiver who is alert for possible side effects. 4. The caregiver must separately meet the specified inclusion/
Exclusion criteria
for caregivers for this Phase 1b Extension Study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety of repeated RB-ADSC treatment in study participants with AD | up to 12 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in ADAS-cog13 | Baseline, Month 6, Month 12 | 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. |
| Change from Baseline in FAST | Baseline, Month 6, Month 12 | 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. |
| Change from Baseline in MoCA | Baseline, Month 6, Month 12 | Mild cognitive impairment and the early onset of dementia will be assessed using the Montreal Cognitive Assessment (MoCA) |
| Change from Baseline in Volumetric MRI with Contrast | Baseline, Month 6 and Month 12 | Volumetric MRI with contrast of the brain will be used to detect and monitor brain abnormalities. |
| Change from Baseline in NeuroQuant MRI | Baseline, Month 6 and Month 12 | NeuroQuant MRI will be used to measure volumes of brain structures. |
| Change from Baseline in Amyloid Positron Emission Tomography (Amyloid-PET) | Baseline, Month 6, Month 12 | Amyloid-PET will be used to quantitatively assess amyloid plaque deposition in the brain |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker pTau | Baseline, Month 6, Month 12 | 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). |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker Total-Tau | Baseline, Month 6, Month 12 | 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). |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker Ab42 | Baseline, Month 6, Month 12 | 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). |
| Change from Baseline in MMSE | Baseline, Month 6, Month 12 | 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. |
| Change from Baseline in cerebrospinal fluid (CSF) biomarker ratios reported as amyloid-tau index (ATI) | Baseline, Month 6, Month 12 | 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). |
Contacts
CONTACTRobert Lynn
Outcome results
None listed