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

Phase 2a Assessment of Safety, Tolerability, and Efficacy of Repeated Dosing of Intracerebroventricular Injections of Ex Vivo Expanded, Autologous Adipose-Derived Stem Cells (RB-ADSCs) in Participants With Mild to Moderate Alzheimer's Disease

The goal of this Phase 2 clinical trial is to learn if repeated dosing of RB-ADSC (an investigational autologous cell product obtained from participant's own adipose tissue) enhances the positive preliminary results seen in Phase 1 for the of treatment for mild to moderate Alzheimer's Disease in adults. The clinical trial will also continue to evaluate the safety of repeated dosing of RB-ADSC. This study will primarily evaluate the effects of repeated dosing of RB-ADSC on cognitive performance compared to placebo control. Participants will receive RB-ADSC every 2 months for a total of 6 doses. Participants randomized into the placebo control group will have the option to cross over to receive treatment after completion of the primary phase of the study.

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.

Inclusion Criteria:

• ≥45 and ≤85 years of age
• Mild to moderate AD diagnosis
• FAST stage 4 or 5
• MMSE 10-23
• Amyloid PET scan centiloid score >30
• ADmark® CSF analysis of ATI (<1.0) and P-Tau (>60)
• No tumors or other disease responsible for dementia
• Participant otherwise in good general health
• Written informed consent from participant or legal representative
• Participant must have caregiver who separately meets specified inclusion/exclusion criteria for caregivers
• Participant must be able to donate adequate amount of lipoaspirate to establish the final product

Exclusion Criteria:

• Taking prohibited medications
• Prior cell therapy implantation
• Existing ventriculoperitoneal shunts
• Neurological disorders except AD
• Psychiatric disorders such as schizophrenia, bipolar/unipolar depression, delirium
• Drug or alcohol abuse in past 2 years
• History of cancer within the past 5 years
• No caregiver available to meet the inclusion criteria for caregivers
• Involvement in other investigational product clinical trial within the past 3 months for monoclonal antibodies, or 6 months for other investigational products