Study to Evaluate the Safety and Efficacy of AstroStem in Treatment of Alzheimer's Disease
Study Details
Study Description
Brief Summary
This is a phase 2b randomized, double-blind, active-controlled study with 2 treatment arms, to compare the efficacy and safety of AstroStem vs. Donepezil 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 and Donepezil Placebo every 4 weeks from Week 0 to Week 16. On the other hand, patients who are randomized into the active control group will receive 5 mg of Donepezil and AstroStem Placebo every 4 weeks from Week 0 to Week 16. After the final administration, patients will be scheduled for two follow-up visits, at Weeks 28 and 40, to assess efficacy and safety endpoints.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment 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 and Donepezil Placebo
Autologous adipose tissue derived mesenchymal stem cells (AdMSCs) and Donepezil Placebo
Other Names:
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| Active Comparator: Active Control Active control group will receive 5 mg of Donepezil and AstroStem Placebo. |
Drug: Donepezil and AstroStem Placebo
Active control group receive 5 mg of Donepezil every 4 weeks from Week 0 to Week 16.
Other Names:
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Outcome Measures
Primary Outcome Measures
- ADAS-Cog (Alzheimer's Disease Assessment Scale-cognitive subscale) [Baseline and 28 Weeks]
Change from baseline to Week 28 in the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog) score. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. A reduction in scores compared to baseline indicates an improvement in cognitive functions.
Secondary Outcome Measures
- MMSE (Mini-mental status examination) [Baseline and 28 Weeks]
Change from baseline to Week 28 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.
- C-SSRS (Columbia Suicide Severity Rating Scale) [Baseline and 28 Weeks]
Change from baseline to Week 28 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.
- NPI (Neuropsychiatric Inventory) [Baseline and 28 Weeks]
Change from baseline to Week 28 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).
- ADCS-CGIC (Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change) [Baseline and 28 Weeks]
Change from baseline to Week 28 in the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) score. The overall condition of the disease change is assessed (improved or deteriorated) by the doctor and the patient, and the 8-point scoring method (0-7 points) was adopted.
- Treatment related Adverse Events [Baseline and 28 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
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female patients aged 50 and above at the time of signing the Informed Consent Form
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Patients who can understand and provide written informed consent (assent)
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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
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Patients who have an MMSE Score of 20 to 24 at baseline
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Patients who have not taken any FDA-approved AD medication (donepezil, galantamine, memantine, rivastigmine or any combination) since their AD diagnosis
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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
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Patients who have a diagnosis of probable mild AD according to concentration of biomarkers in CSF (Amyloid beta 42, t-tau and p-tau)
Exclusion Criteria:
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Female patients who are pregnant, nursing, or of childbearing potential while not practicing effective contraception
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Patients who have signs of delirium
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Patients who have had a cortical stroke within the preceding 2 years
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Patients who have a prolonged QTc interval at screening; >450 msec for males or >470 msec for females
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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
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Patients who have a diagnosis of dementia or cause of cognitive impairment other than AD
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Patients who have a significant abnormal result in laboratory tests, in the opinion of the investigator
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Patients who have participated in any investigational drug, stem cell therapy, or device trial within the previous 3 months at screening
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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
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Patients who are known to have autosomal dominant mutation-associated presenile AD
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Patients who show signs of Acquired Immunodeficiency Syndrome (AIDS), Hepatitis B Virus (HBV), Hepatitis C (HCV), Venereal Disease Research Laboratory (VDRL)
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Patients who have any conditions that would contraindicate an MRI, such as the presence metallic objects in the eyes, skin, or heart
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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
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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)
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Patients who have suspected active lung disease based on chest X-ray
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Patients who are hypersensitive to fetal bovine serum or penicillin
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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)
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Patients for whom the investigator judges the liposuction may cause a problem
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Nature Cell Co. Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AST-ADP2-US02