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

Study Overview
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Brief Summary
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This is a phase 2b randomized, double-blind, Placebo-controlled study with 2 treatment arms, to compare the efficacy and safety of AstroStem vs. Placebo treatment in patients with mild Alzheimer's Disease(AD). Eligible patients diagnosed with AD within one year of the start of treatment will be enrolled. Patients who are randomized into the treatment group will be administered via intravenously AstroStem every 4 weeks from Week 0 to Week 36. On the other hand, patients who are randomized into the placebo control group will receive Placebo every 4 weeks from Week 0 to Week 36. After the final administration, patients will be scheduled for two follow-up visits, at Weeks 44 and 52, to assess efficacy and safety endpoints.

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

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: AstroStem
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 50 and above at the time of signing the Informed Consent Form Patients who can understand and provide written informed consent (assent) Patients who have a diagnosis of probable mild Alzheimer's Disease(AD) according to the National Institute of Neurological and Communicative Disorders and Stroke; Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria within one year of the start of treatment Patients who have an MMSE Score of 20 to 24 at screening Patients who have a Clinical Dementia Rating (CDR)-Global Score of 0.5 to 1 at baseline Patients who have any FDA-approved AD medication (donepezil, galantamine, memantine, rivastigmine or any combination) since their AD diagnosis receiving a stable dose of medical teratment for at least 12 weeks prior to Screening and were to stay on a stable dose during the study Patients who have one (or more) identified adult caregiver (study partner) who is able to read, understand, and speak the designated language at the study site; who either lives with the subject or sees the subject for ≥2 hours/day ≥4 days/week; and who agrees to accompany the subject to each study visit and to participate in the subject's clinical assessments Patients who have a diagnosis of probable mild AD according to Amyloid PET scan at screening Exclusion Criteria: Female patients who are pregnant, nursing, or of childbearing potential while not practicing effective contraception Patients who have signs of delirium Patients who have had a cortical stroke within the preceding 2 years Patients who have a prolonged QTc interval at screening; >450 msec for males or >470 msec for females Patients who have a 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 Patients who have a diagnosis of dementia or cause of cognitive impairment other than AD Patients who have a significant abnormal result in laboratory tests, in the opinion of the investigator Patients who have participated in any investigational drug, stem cell therapy, or device trial within the previous 3 months at screening Patients 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 Patients who are known to have autosomal dominant mutation-associated presenile AD Patients who show signs of Acquired Immunodeficiency Syndrome (AIDS), Hepatitis B Virus (HBV), Hepatitis C (HCV), Venereal Disease Research Laboratory (VDRL) Patients who have any conditions that would contraindicate an MRI, such as the presence metallic objects in the eyes, skin, or heart Patients 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 Patients 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) Patients who have suspected active lung disease based on chest X-ray Patients who are hypersensitive to fetal bovine serum or penicillin Patients 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) Patients for whom the investigator judges the liposuction may cause a problem

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>Treatment group will be administered via intravenously AstroStem which consists of two syringes and each syringe contains 2.0 x 10^8 cells / 20 mL of saline with 30% auto-serum. | Drug: AstroStem<br>* Treatment group receive AstroStem(Autologous adipose tissue derived mesenchymal stem cells, AdMSCs) every 4 weeks from Week 0 to Week 36.<br>|
| Placebo Comparator: Placebo Control<br>Placebo control group will receive AstroStem Placebo. | Drug: Placebo<br>* Placebo control group receive 20 mL of Saline and auto serum every 4 weeks from Week 0 to Week 36.<br>* Other names: AstroStem Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SUVR (Standard Uptake Value Ratio) | Standard Uptake Value Ratio (SUVR) of the Amyloid PET scan | Baseline and 52 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CDR-SB score (Clinical Dementia Rating Sum of Boxes) | Changes of CDR-SOB from baseline at Week 52 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 52 Weeks | 
| ADAS-Cog-11 score (Alzheimer's Disease assessment Scale-Cognitive Subscale (11 items)) | Change of ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) from Baseline at Week 52 Score range: 0-70 A score of 70 represents the most severe impairment and 0 represents the least impairment | Baseline and 52 Weeks | 
| MMSE (Mini-mental status examination) | Change from baseline to Week 52 in the Mini-mental status examination (MMSE) score. The Mini-Mental State Exam (MMSE) is a widely used test of cognitive function among the elderly; it includes tests of orientation, attention, memory, language and visual-spatial skills. The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. | Baseline and 52 Weeks | 
| ADCS-ADL-MCI (Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory) | Change from baseline to Week 52 in the ADCS-ADl MCI 0-53 A score of 0 represents the most severe impairment and 53 represents the least impairment | Baseline and 52 Weeks | 
| C-SSRS (Columbia Suicide Severity Rating Scale) | Change from baseline to Week 52 in the Columbia Suicide Severity Rating Scale (C-SSRS) score. The suicidal ideation severity subscale ranges from 1 to 5 (with higher number indicating more severe ideation). The intensity of ideation subscale includes 5 questions each one ranging from 1 to 5 (with higher number indicating more intense ideation). The suicidal behavior subscale includes 4 yes/no questions. The suicidal behavior lethality subscale inquires about the level of actual or potential medical damage. | Baseline and 52 Weeks | 
| NPI (Neuropsychiatric Inventory) | Change from baseline to Week 52 in the Neuropsychiatric Inventory (NPI) score. The NPI is a structured interview with a caregiver or qualified study partner (defined as having direct contact > 2 days/week) that evaluates both presence and severity of 12 neuropsychiatric features which include: delusions, hallucinations, dysphoria, anxiety, agitation/aggression, euphoria, disinhibition, irritability, lability, apathy, aberrant motor behavior, night-time behavior, and appetite/ eating changes. If the response to the domain question is No, the informant goes to the next question. If Yes, the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale ranging from 1 to 3 (mild to severe). | Baseline and 52 Weeks | 
| 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 | Baseline and 52 Weeks |