Clinical trial NCT05667649: Autologous Activated Adipose-derived Stem Cells (RB-ADSC) Injected Directly Into the Brain for Mild to Moderate Alzheimer's Disease
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Alzheimer Disease
Keywords: Alzheimer's Disease
AD
Autologous
Stem cells
Lead sponsor: Regeneration Biomedical, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-28
Enrollment: 18
Sex: ALL
Minimum age (years): 45
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The safety of RB-ADSC treatment in study participants with AD
timeFrame: up to 28 weeks
Secondary outcomes:
measure: Change from Baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog)
timeFrame: up to 52 weeks
measure: Change from Baseline in Mini Mental State Examination (MMSE)
timeFrame: up to 52 weeks
Other outcomes:
Locations:
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital Presbyterian
state: California
Study officials:
References:
citation: Duma C, Kopyov O, Kopyov A, Berman M, Lander E, Elam M, Arata M, Weiland D, Cannell R, Caraway C, Berman S, Scord K, Stemler L, Chung K, Khoudari S, McRory R, Duma C, Farmer S, Bravo A, Yassa C, Sanathara A, Singh E, Rapaport B. Human intracerebroventricular (ICV) injection of autologous, non-engineered, adipose-derived stromal vascular fraction (ADSVF) for neurodegenerative disorders: results of a 3-year phase 1 study of 113 injections in 31 patients. Mol Biol Rep. 2019 Oct;46(5):5257-5272. doi: 10.1007/s11033-019-04983-5. Epub 2019 Jul 20.