A Study to Evaluate the Safety and Efficacy of AstroStem in Treatment of Alzheimer's Disease

Study Overview
=================
Brief Summary
-----------------
This is a randomized, double-blind, placebo-controlled, parallel-group comparison study in subjects with Alzheimer's Disease. Following first screening period, subjects will be randomly assigned into one of the following arms: AstroStem and placebo control in a 1:1 ratio. AstroStem or placebo control will be administered via I.V. at Week 0. This procedure will be repeated 9 times at 2-week interval. Subjects will be scheduled for two follow-up visits at Weeks 30 and 52 to evaluate primary and secondary outcome endpoints.

Official Title
-----------------
A Phase 1/2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of AstroStem, Autologous Adipose Tissue Derived Mesenchymal Stem Cells, in Patients With Alzheimer's Disease

Conditions
-----------------
Alzheimer Disease

Intervention / Treatment
-----------------
* Drug: AstroStem
* Other: Placebo-Control


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects aged 50 and above at the time of signing the Informed Consent form Subjects who can understand and provide written informed consent (assent) Subjects who have diagnosis of probable mild-to-moderate Alzheimer disease according to NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association) criteria Subjects who have MMSE Score of 16 to 26 at screening Subjects who are taking FDA-approved AD medications (donepezil, galantamine, memantine, rivastigmine or their combinations) treatment on a stable dosage for at least 3 months prior to screening. Subjects who have one (or more) identified adult caregiver who is able to read, understand, and speak the designated language at the study site; either lives with the subject or sees the subject for ≥2 hours/day ≥4 days/week; and agrees to accompany the subject to each study visit Subjects who have a designated study partner who will accompany the subject to all clinic visits and participate in the subject's clinical assessments Exclusion Criteria: Subjects who are females who are pregnant, nursing, or of childbearing potential while not practicing effective contraception Subjects who have signs of delirium Subjects who have had cortical stroke within the preceding 2 years Subjects who have a prolonged QTc interval; >450 msec in male or >470 msec in female at screening Subjects who have diagnosis of severe white matter hyperintensity (WMH), which is defined as ≥ 25mm of the deep white matter and ≥ 10mm of the periventricular capping/banding in lengths Subjects who have diagnosis of dementia or cause of cognitive impairment other than Alzheimer's disease Subjects who have a significant abnormal result in laboratory tests, in the opinion of the investigator Subjects who have participated in any investigational drug, stem cell therapy, or device trial within the previous 3 months at screening Subjects with any current psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the subject´s ability to complete the study Subjects who are known to have autosomal dominant mutation-associated presenile AD Subjects who show signs of AIDS (Acquired Immunodeficiency Syndrome), HBV (Hepatitis B Virus), HCV (Hepatitis C), VDRL (Venereal Disease Research Laboratory) Subjects who have any conditions that would contraindicate an MRI, such as the presence metallic objects in the eyes, skin, or heart Subjects who have > 4 cerebral microhemorrhages (regardless of their anatomical location or diagnostic characterization as possible or definite), a single area of superficial siderosis, or evidence of a prior microhemorrhage as assessed by MRI Subjects who have history of malignant cancer within the last 5 years (The following is a partial list of conditions that are permissible for study entry: non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical, or non-progressive prostate cancer) Subjects who have suspected active lung disease based on chest X-ray Subjects who are hypersensitive to fetal bovine serum or penicillin Subjects who are currently using immunosuppressants, cytotoxic drug, corticosteroids or similar steroidal anti-inflammatory medication (e.g., Prednisone) on a regular basis (exceptions allowed include; regular use of steroidal nasal sprays, topical steroids, and estrogen-replacement therapy) Subjects for whom the investigator judges the liposuction can cause any problems Subjects who have history of local anesthetic allergy

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AstroStem<br> | Drug: AstroStem<br>* Autologous adipose tissue derived mesenchymal stem cells (AdMSC)<br>|
| Placebo Comparator: Placebo-Control<br> | Other: Placebo-Control<br>* Saline with 30% auto-serum<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Related Adverse Events | Number of subjects with treatment related adverse events as assessed by analysis of adverse events including symptoms, and abnormal findings on physical examination, vital signs, ECG, and standard laboratory examination results | 30 Weeks | 
| ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive Subscale) | Change of ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) from Baseline at Week 30 Score range: 0-70 A score of 70 represents the most severe impairment and 0 represents the least impairment | Baseline and 30 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MMSE (Mini-mental Status Examination) | Change of MMSE from baseline at Week 30 Score range: 0-30 A score of 20 to 24 suggests mild dementia, 13 to 20 suggests moderate dementia, and less than 12 indicates severe dementia. | Baseline and 30 Weeks | 
| CDR-SOB (Clinical Dementia Rating-Sum of Boxes) | Changes of CDR-SOB from baseline at Week 30 Score range: 0-18.0 0 = normal, 0.5-4.0 = questionable cognitive dementia, 4.5-9.0 = mild dementia, 9.5-15.5 = moderate dementia, and 16.0-18.0 = severe dementia | Baseline and 30 Weeks | 
| NPI (Neuropsychiatric Inventory) | Changes of NPI from baseline at Week 30 Score range: 0-144 higher score indicates higher disturbance. | Baseline and 30 Weeks | 
| GDS (Geriatric Depression Scale) | Changes of GDS from baseline at Week 30 Score range: 0-15 Scores of 0-4 are considered normal, depending on age, education, and complaints; 5-8 indicate mild depression; 9-11 indicate moderate depression; and 12-15 indicate severe depression. | Baseline and 30 Weeks | 
| ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) | Change of ADCS-ADL from baseline at Week 30 Score range: 0-78 Lower score indicates greater severity. | Baseline and 30 Weeks | 
| C-SSRS (Columbia Suicide Severity Rating Scale) | Changes of C-SSRS from baseline at Week 30 Score range: 0-25 Higher score indicates higher severity. | Baseline and 30 Weeks |