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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 115
- 主要终点
- Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Composite Score
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 45 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •≥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/
排除标准
- •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
研究组 & 干预措施
RB-ADSC low dose
Participants will receive repeated doses of 2.5x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir
干预措施: RB-ADSC (Biological)
RB-ADSC high dose
Participants will receive repeated doses of 5x10^6 RB-ADSC infused in the previously implanted Ommaya reservoir
干预措施: RB-ADSC (Biological)
Placebo control
Participants will receive placebo comparator in the previously implanted Ommaya reservoir
干预措施: Placebo (Other)
结局指标
主要结局
Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Composite Score
时间窗: Baseline, Month 6 and Month 12
iADRS will be used to assess whether RB-ADSC slows down the clinical decline associated with AD compared with placebo. iADRS evaluates cognition and daily function performance by combining items from the ADAS-Cog13 and the Alzheimer's disease cooperative study-instrumental activities of daily living scale (ADCS-iADL). The scale ranges from 0 to 144, where lower scores indicate worse performance and higher score indicates better performance.
次要结局
- Change from Baseline in CSF Biomarkers(Baseline, Month 6 and Month 12)
- Change from Baseline in MMSE(Baseline, Month 6 and Month 12)
- Change from Baseline in ADAS-cog13(Baseline, Month 6 and Month 12)
- Change from Baseline in Amyloid Positron Emission Tomography (Amyloid-PET)(Baseline, Month 6 and Month 12)
- Change from Baseline in FAST(Baseline, Month 6 and Month 12)
- Change from Baseline in ADCS-iADL(Baseline, Month 6 and Month 12)
- Change from Baseline in CDR-SB(Baseline, Month 6 and Month 12)
- Change from Baseline in Volumetric MRI with Contrast(Baseline, Month 6 and Month 12)
- Change from Baseline in NeuroQuant MRI(Baseline, Month 6 and Month 12)
- Safety of Repeated Dosing RB-ADSC(Up to Month 16)