Follow-up Study of Safety and Efficacy in Subjects Who Completed NEUROSTEM® Phase-I/IIa Clinical Trial.

Study Overview
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Brief Summary
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A long-term follow-up study to obtain safety and efficacy data in subjects who completed phase 1/2a clinical trial of NEUROSTEM® (NCT02054208), comparing NEUROSTEM and placebo groups for up to 36 months after the initial administration in patients suffering from Alzheimer's disease

Detailed Description
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The subjects will be followed up at 12-month, 24-month, and 36-month (phone call) after the initial administration of NEUROSTEM®.

Official Title
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Follow-up Study of Safety and Efficacy in Subjects Who Completed 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
* Other: Normal saline 2mL


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assessment of safety and exploratory treatment efficacy in subjects who were enrolled and completed phase 1/2a clinical trial of NEUROSTEM®. Subjects who have been treated with either NEUROSTEM® or placebo at least 12 months ago. 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: Subjects who were not enrolled in phase 1/2a clinical trial of Neurostem® for assessing safety and exploratory treatment efficacy Other subjects, excluding those listed above, who were deemed unsuitable by the PI

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 86 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NEUROSTEM® (hUCB-MSCs)- low dose<br>human umbilical cord blood derived mesenchymal stem cells Low dose: 1 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals | Biological: human umbilical cord blood derived mesenchymal stem cells<br>* Low dose: 1 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals High dose: 3 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals<br>* Other names: NEUROSTEM®;|
| 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>* Low dose: 1 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals High dose: 3 x 10^7cells/2mL 3 repeated intraventricular administrations via an Ommaya Reservoir at 4 week intervals<br>* Other names: NEUROSTEM®;|
| Placebo Comparator: Placebo<br>normal saline 2mL, doses separated by 4 weeks for a total of 3 doses | Other: Normal saline 2mL<br>* Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations<br>|

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 | Alzheimer's Disease assessment Scale-Cognitive Subscale | 24 month after the first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from the baseline in S-IADL | Seoul Instrumental Activities of Daily Living | 24 month after the first dose | 
| Change from the baseline in K-MMSE | Mini Mental State Exmination Korean version | 24 month after the first dose | 
| Change from the baseline in CGA-NPI | Caregiver-administered Neuropsychiatric Inventory | 24 month after the first dose | 
| ADAS-Cog Response Rate | the ADAS-cog score at 24 month after the first administration compared to the baseline | 24 month after the first dose | 
| Change in CDR-SOB | Clinical Dementia Rating-Sum of Box | 24 month after the first dose | 
| Change in CIBIC-plus | The Clinician's Interview Based Impression of Change-plus | 24 month after the first dose | 
| Change in Florbetaben-PET | Florbetaben - Pittsburgh Compound B-positron emission tomography | 24 month after the first dose | 
| Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose) | fluorodeoxyglucose positron emission tomography | 24 month after the first dose | 
| Change from baseline in MRI (DTI mapping) | MRI Analysis | 24 month after the first dose | 
| Change from the baseline in CSF biomarkers | biomakrer analysis | 24 month after the first dose |