Exploratory Efficacy Study of NEUROSTEM® in Subjects Who Control Group of NEUROSTEM®

Study Overview
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Brief Summary
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This study is to evaluate of Exploratory Efficacy of NEUROSTEM® in Subjects who control group of NEUROSTEM® Phase-I/IIa Clinical Trial

Official Title
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Exploratory Efficacy Study of NEUROSTEM® in Subjects Who Control Group of NEUROSTEM® Phase-I/IIa Clinical Trial

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Biological: human umbilical cord blood derived mesenchymal stem cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who have been treated with placebo in phase 1/2a clinical trial of NEUROSTEM® Subjects who voluntarily decided to participate and signed the consent form after receiving explanations on the clinical trial (in case it is difficult for the participant to sign, the consent of the legal representative) Exclusion Criteria: 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 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 Bleeding disorder (abnormal blood coagulation test result (i.e. platelet count of < 137,000/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) Contraindicated for any of the tests performed during the clinical trial period (for example, MRI, CT, PET) Whom the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEUROSTEM (hUCB-MSCs) - high dose<br>human umbilical cord blood-derived mesenchymal stem cells High dose: 3 x 10^7 cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4-week intervals | Biological: human umbilical cord blood derived mesenchymal stem cells<br>* High dose: 3 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4-week intervals<br>* Other names: NEUROSTEM;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from the baseline in ADAS-Cog | The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation, and praxis using an 11-point AD Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. | 4weeks,8weeks,12weeks,24 weeks after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CDR-SOB | The CDR-SOB(Clinical Dementia Rating, Sum of Boxes) is a global rating of dementia severity based on the clinician's interpretation of the history and examination. The range of this instrument is 0 to 18 with higher numbers indicating greater impairment. | 24 weeks after the first dose | 
| Change from the baseline in K-MMSE(korean version) | The MMSE(Mini-Mental State Examination) is a brief, practical test for cognitive dysfunction. The test consists of five sections (orientation, registration, attention-calculation, recall, and language) and results in a total possible score from 0 to 30, with higher scores indicating better function | 24 weeks after the first dose | 
| Change from the baseline in CGA-NPI | Caregiver-administered Neuropsychiatric Inventory, Measure abnormal behavior. The score range is 0-144. A higher score means severe abnormal behavior. | 24 weeks after the first dose | 
| Change from the baseline in SIB | The Severe Impairment Battery (SIB) is an assessment of cognitive dysfunction across nine domains such as memory, language, and orientation. The score ranges from 0 (worst) to 100 (best) | 24 weeks after the first dose | 
| ADAS-Cog Response Rate | Alzheimer's Disease assessment Scale-Cognitive Subscale | The ADAS-cog response is defined as no worsening (no change or improvement on ADAS-cog score) of the ADAS-cog score at 24 weeks after the first administration compared to the baseline | 
| Change in CIBIC-plus | The Clinician's Interview-Based Impression of Change-plus(CIBIC-plus) is a rating scale derived from an interview with the patient and caregiver with an independent rater designed to measure several domains of patient function, such as mental/cognitive state, behavior, and activities of daily living. The scores range from 1 (marked improvement) to 7 (marked worsening). | 24 weeks after the first dose | 
| Change from the baseline in CSF biomarkers | biomakrers analysis (Amyloid beta 42, Phosphorylated tau, Total tau, RBC, WBC, Protein, Glucose) | 24 weeks after the first dose |