Safety and Exploratory Efficacy Study of NEUROSTEM® Versus Placebo in Patients With Alzheimer's Disease

The study is divided into the 2 stages: dose-escalation in stage 1 and randomized and multiple-dose cohort parallel design in stage 2.The target population for enrollment in this study is patients with mild to moderate Alzheimer's disease.

1 stage Inclusion Criteria:

• Korean male or female at 50 -85 years of age
• Diagnosis of Probable Alzheimer type according to NINCDS-ADRDA criteria at Visit 1 (Screening)
• Korea Mini-Mental State Examination (KMMSE) score of 18 - 26 at Visit 1 (Screening)
• Positive for Amyloid on PIB-PET or Florbetaben PET
• A subject who is informed of the clinical trial and signs a consent form (if unable to sign, a consent from a legally acceptable representative is required)

2 stage Inclusion Criteria:

• Korean male or female at 50 -85 years of age
• Diagnosis of Probable Alzheimer type or mild cognitive impairment due to Alzheimer's disease (stage A) according to NIA-AA criteria at Visit 1(Screening)
• Korea Mini-Mental State Examination (KMMSE) score of over 18 at Visit 1 (Screening)
• Positive for Amyloid on Florbetaben PET
• A subject with neurodegeneration (mild atrophy of the brain) as confirmed by MRI
• A subject who is informed of the clinical trial and signs a consent form (if unable to sign, a consent from a legally acceptable representative is required)

Exclusion criteria

• Concurrent mental disorder (such as schizophrenia, depression, bi-polar diseases or others) aside from dementia
• Concurrent dementia as a result of other neurodegenerative disorders (due to infectious disease of the central nervous system such as HIV, syphilis), head injury, Creutzfeld-Jacob disease, Pick's disease, Huntington's disease, or Parkinson's disease
• Diagnosis of severe white matter hyperintensitivity (WMH) according to CREDOS (Clinical REsearch Center for Dementia of South Korea), which is defined as ≥ 25mm of the deep white matter and ≥ 10mm of the periventricular capping/banding in lengths
• History of stroke within 3 months prior to study enrollment
• Severe liver disorder (equivalent to double the normal values of ALT and AST) at Visit 1
• Severe kidney disorder (serum creatinine ≥1.5mg/dL) at Visit 1
• Pregnant or lactating females
• Abnormal Laboratory findings at Visit 1

• Hemoglobin < 9.5 g/dL for male and <9.0 g/dL for female
• Total WBC Count < 3000/mm3
• Total Bilirubin >= 3 mg/dL
• Suspected active lung disease based on chest X-ray at Visit 1
• Woman of childbearing age who refuses to practice medically acceptable contraceptive method (post menopausal patient with no menstruation for at least 12 months is considered as infertile)
• History of screening failure for the clinical trial of NEUROSTEM® in the past 6 months
• Participation in another clinical trial in the past 3 months prior to the beginning (Week 0) of this clinical trial
• Bleeding disorder (abnormal blood coagulation test result (i.e. platelet count of < 150,000/mm3, PT ≥ 1.5 INR, or aPTT ≥ 1.5 x control anti-coagulant or anti-platelet, without anticoagulant or anti-platelet therapy)
• Diagnosis of cancer (of any body system, including brain tumor)
• Substance/alcohol abuse
• Contraindicated for any of the tests performed during the clinical trial period (for example, MRI, CT, PET)
• A subject in whom Ommaya reservoir insertion is considered difficult
• Whom the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above