Alzheimer Disease
Conditions
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.
Interventions
DRUGAstroStem
Autologous adipose tissue derived mesenchymal stem cells (AdMSC)
OTHERPlacebo-Control
Saline with 30% auto-serum
Sponsors
Nature Cell Co. Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Related Adverse Events | 30 Weeks | 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 |
| ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive Subscale) | Baseline and 30 Weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| NPI (Neuropsychiatric Inventory) | Baseline and 30 Weeks | Changes of NPI from baseline at Week 30 Score range: 0-144 higher score indicates higher disturbance. |
| GDS (Geriatric Depression Scale) | Baseline and 30 Weeks | 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. |
| MMSE (Mini-mental Status Examination) | Baseline and 30 Weeks | 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. |
| C-SSRS (Columbia Suicide Severity Rating Scale) | Baseline and 30 Weeks | Changes of C-SSRS from baseline at Week 30 Score range: 0-25 Higher score indicates higher severity. |
| ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) | Baseline and 30 Weeks | Change of ADCS-ADL from baseline at Week 30 Score range: 0-78 Lower score indicates greater severity. |
| CDR-SOB (Clinical Dementia Rating-Sum of Boxes) | Baseline and 30 Weeks | 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 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| AstroStem AstroStem: Autologous adipose tissue derived mesenchymal stem cells (AdMSC) | 11 |
| Placebo-Control Placebo-Control: Saline with 30% auto-serum | 10 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 4 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Placebo-Control | Total | AstroStem |
|---|---|---|---|
| Age, Continuous | 75.6 years STANDARD_DEVIATION 8.2 | 73.9 years STANDARD_DEVIATION 7.6 | 72.4 years STANDARD_DEVIATION 7.6 |
| BMI | 22.8 kg/m^2 STANDARD_DEVIATION 3.5 | 24.6 kg/m^2 STANDARD_DEVIATION 4.3 | 26.3 kg/m^2 STANDARD_DEVIATION 4.3 |
| Height | 168.3 cm STANDARD_DEVIATION 9.7 | 168.1 cm STANDARD_DEVIATION 12.1 | 167.9 cm STANDARD_DEVIATION 14.4 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 1 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 3 Participants | 2 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Not-Hispanic or Latino | 9 Participants | 18 Participants | 9 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 9 Participants | 19 Participants | 10 Participants |
| Sex: Female, Male Female | 5 Participants | 9 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
| Weight | 64.6 kg STANDARD_DEVIATION 12 | 69.9 kg STANDARD_DEVIATION 15.5 | 74.8 kg STANDARD_DEVIATION 17.2 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 3 / 11 | 2 / 10 |
| serious Total, serious adverse events | 3 / 11 | 1 / 10 |
Outcome results
Primary
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
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive Subscale) | 5.9 score on a scale | Standard Deviation 6.8 |
| Placebo-Control | ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive Subscale) | 3.0 score on a scale | Standard Deviation 5.4 |
Primary
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
Time frame: 30 Weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| AstroStem | Treatment Related Adverse Events | 6 Participants |
| Placebo-Control | Treatment Related Adverse Events | 3 Participants |
Secondary
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.
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) | -4.4 score on a scale | Standard Deviation 9 |
| Placebo-Control | ADCS-ADL (Alzheimer's Disease Cooperative Study Activities of Daily Living) | -4.7 score on a scale | Standard Deviation 9.8 |
Secondary
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
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | CDR-SOB (Clinical Dementia Rating-Sum of Boxes) | 1.3 score on a scale | Standard Deviation 1.7 |
| Placebo-Control | CDR-SOB (Clinical Dementia Rating-Sum of Boxes) | 0.9 score on a scale | Standard Deviation 1.5 |
Secondary
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.
Time frame: Baseline and 30 Weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | C-SSRS (Columbia Suicide Severity Rating Scale) | -2.1 score on a scale | Standard Deviation 6.6 |
| Placebo-Control | C-SSRS (Columbia Suicide Severity Rating Scale) | 0.0 score on a scale | Standard Deviation 0 |
Secondary
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.
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | GDS (Geriatric Depression Scale) | -0.3 score on a scale | Standard Deviation 1.3 |
| Placebo-Control | GDS (Geriatric Depression Scale) | 0.3 score on a scale | Standard Deviation 2.1 |
Secondary
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.
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | MMSE (Mini-mental Status Examination) | -3.4 score on a scale | Standard Deviation 2.8 |
| Placebo-Control | MMSE (Mini-mental Status Examination) | -1.4 score on a scale | Standard Deviation 2.8 |
Secondary
NPI (Neuropsychiatric Inventory)
Changes of NPI from baseline at Week 30 Score range: 0-144 higher score indicates higher disturbance.
Time frame: Baseline and 30 Weeks
Population: 3 of the 11 astrostem groups were dropped out and 1 was violated protocol.~1 of the 10 Placebo-control groups was dropped out and 2 were violated protocol.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| AstroStem | NPI (Neuropsychiatric Inventory) | -1.4 score on a scale | Standard Deviation 8.5 |
| Placebo-Control | NPI (Neuropsychiatric Inventory) | -5.7 score on a scale | Standard Deviation 11.5 |