Study of Intracerebroventricular Injections of Autologous Adipose-Derived Stem Cells (RB-ADSCs) in Participants With Mild-Moderate Alzheimer's Disease

This is a randomized, placebo-controlled, dose range finding for safety and efficacy, Phase 2a U.S. multicenter study of repeated administration of RB-ADSC in participants with mild to moderate Alzheimer's Disease AD. RB ADSC consists of stem cells obtained from the participant's own adipose tissue by lipoaspirate that have been cultured and expanded outside the body, enriched for Wnt-activated cells, and prepared for administration into the same participant. An Ommaya reservoir, which is an intraventricular catheter system, will be implanted under the scalp for intraventricular administration of RB-ADSC.

Approximately 115 adult participants are expected to be enrolled in this Phase 2a study. Participants will be randomized at a 4:1 ratio of RB-ADSC treatment to placebo. Participants randomized into the RB-ADSC treatment arm will be subsequently randomized with a 1:1 ratio to a treatment dose level: low-dose RB-ADSC (2.5 x 10\^6 cells), and high-dose RB-ADSC (5.0 x 10\^6 cells), for an overall randomization scheme of 2:2:1.

RB-ADSC will be delivered intracerebroventricularly every 2 months via the previously implanted Ommaya reservoir for a treatment duration of 10 months (inclusive of 10th month; up to 6 injections in total). Participants will be followed for 6 months after the last administration. The primary and secondary objectives will evaluate the efficacy based on cognitive, functional and CSF biomarker (Phospho-Tau, Total Tau, AB-42) assessments. Additionally, safety evaluations, volumetric MRI (Neuro Quant®) assessment, and diagnostic imaging comparison (Amyloid PET) will be performed.

After completing the Month 12 evaluation, participants in the placebo arm will be allowed to cross over to receive RB-ADSC. Participants in the cross-over will be randomized to a treatment dose level (low dose or high dose) at a 1:1 ratio. Cross-over participants will receive RB-ADSC doses every 2 months for a treatment duration of 10 months.

• Change from Baseline in CSF Biomarkers [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in MMSE [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in ADAS-cog13 [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in FAST [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in ADCS-iADL [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in CDR-SB [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in Amyloid Positron Emission Tomography (Amyloid-PET) [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in Volumetric MRI with Contrast [Срок оценки: Baseline, Month 6 and Month 12]
• Change from Baseline in NeuroQuant MRI [Срок оценки: Baseline, Month 6 and Month 12]
• Safety of Repeated Dosing RB-ADSC [Срок оценки: Up to Month 16]