Evaluation of the Safety and Potential Therapeutic Effects After Intravenous Transplantation of CB-AC-02 in Patients With Alzheimer's Disease

Study Overview
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Brief Summary
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The objective of the study is to evaluate the safety and the potential therapeutic effects of CB-AC-02 Intravenous Transplantation in patients with Alzheimer' disease comprised of 2 treatment cohorts:

Official Title
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A Randomized, Double-blind, Placebo-controlled, Phase I / IIa Clinical Trial for Evaluation of Safety and Potential Therapeutic Effect After Transplantation of CB-AC-02 in Patients With Alzheimer's Disease

Conditions
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Alzheimer's Disease

Intervention / Treatment
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* Biological: CB-AC-02
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Korean male or female at 50+ years of age at the time of screening visit Diagnosis of Probable Alzheimer disease (probable AD) according to NINCDS-ADRDA criteria at Screening visit Positive for Amyloid on amyloid-ligand PET A subject with the imaging findings of Alzheimer's disease as confirmed by MRI or PET Presence of brain atrophy on brain MRI by visual assessment Presence of reduced brain glucose metabolism in bilateral temporal-parietal lobe on FDG-PET Korea Mini-Mental State Examination (KMMSE) score of 10-26 at time of screening visit Presence of caregiver who can provide information on the subject's condition Subject who has been taking stable dose of Alzheimer medication for last 2 months or more 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 Dementia as a result of other disorders [i.e. infectious disease of the central nervous system such as HIV, syphilis, head injury, Creutzfeld-Jacob disease, Picks disease, Huntington's disease, Parkinson's disease, other subdural hematoma, hydrocephalus and structural brain lesions, drug addiction, alcoholism, substance abuse, thyroid disease, parathyroid disease, vitamins and other nutritional deficiencies and vascular etc.] Subject with vascular dementia as determined by the clinical criteria of DSM-IV and the imaging criteria of Erkinkuntii Subject with severe white matter hyperintensities (i.e. ≥ 25mm of the deep white matter and ≥ 10mm of the periventricular capping/banding in lengths) Abnormal laboratory findings at screening visit: A. ALT or AST ≥ 2.5 times the upper limit of normal value B. Serum creatinine ≥ 1.5 times the upper limit of normal value C. Total bilirubin ≥ 2 times the upper limit of normal value D. Total WBC counts < 3,000/㎣ E. Hemoglobin <9.5g/dL in men or <9.0g/dL in women F. Platelet count < 150,000/㎣ at screening visit G. PT (INR) ≥ 1.5 or aPTT ≥ 1.5 times the upper limit of normal value Subjects who are positive for HIV, syphilis or active HBV, HCV infection Subjects in poor medical condition or subjects with severe cardiovascular, gastrointestinal, pulmonary or endocrinologic disease A. Suspected active active lung disease on chest X-ray at screening visit B. Diagnosis of cancer (except for the subjects who remains in complete remission for 5 years or more ) Subject with concurrent unstable psychiatric disorder (i.e. severe depression, or schizophrenia, or bipolar disorder, etc) Pregnant or lactating women Women of childbearing age who reject to practice contraception with one of the following methods Use a condom Use of contraceptive (oral, dermal, or injectable) Use an intra-uterine contraceptive device Subjects with a history of alcohol abuse (>30g/day) or drug abuse Subjects who cannot undergo any of the tests performed in this clinical trial (for example, MRI, CT, PET, CSF study) Subjects with known allergies to protein products (Bovine serum), antibiotics (gentamycin) or DMSO Subjects whom the principal investigator considers inappropriate for participation in theis study

Ages Eligible for Study
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Minimum Age: 50 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CB-AC-02<br>Subjects with Alzheimer's disease Intervention: CB-AC-02 | Biological: CB-AC-02<br>* Stage1: ① Group1: CB-AC-02, 2.0 x 10^8 cells on day 0 ② Group2: CB-AC-02, 2.0 x 10^8 cells, on day 0 and on week 4 (repeated injection) Stage2 ① Arm1: K-MMSE 20 26 CB-AC-02, 2.0 x 10^8 cells on day 0 and on week 4 (repeated injection) ② Arm2: K-MMSE 10 19 CB-AC-02, 2.0 x 10^8 cells on day 0 and on week 4 (repeated injection)<br>|
| Placebo Comparator: Placebo<br>Subjects with Alzheimer's disease Intervention: Placebo | Biological: Placebo<br>* Stage2: Placebo on day 0 and on week 4 (repeated injection)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Adverse Events | Number of subjects with treatment-related adverse events. The safety and tolerability of treatment with CB-AC-02 will be assessed by analysis of adverse events, abnormal findings on physical examinations, standard laboratory tests. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes from the baseline in ADAS-Cog (Azheimer's disease Assessment Scale - Congintive Subscale) Score |  | 48 weeks | 
| Changes from the baseline in K-MMSE (Korean-Mini Mental Status Examination) Score |  | 48 weeks | 
| Changes from the baseline in GDS (Global Deterioration Scale) |  | 48 weeks | 
| Changes from the baseline in CDR (Clinical Dementia Rating) Score |  | 48 weeks | 
| Changes from the baseline in K-IADL (Korean Instrumental Activities of Daily Living) Score |  | 48 weeks | 
| Changes from the baseline in CGA-NPI (Caregiver Administered-Neuropsychiatric Inventory) Score |  | 48 weeks | 
| Change in CIBIC (Clinician Interview Based Impression of Change)-plus |  | 48 weeks | 
| Changes from the baseline in SF-36 |  | 48 weeks | 
| Changes in Amyloid Beta and Tau amount (pg/mL) in CSF (Cerebrospinal fluid) |  | 48 weeks | 
| Change in Brain MRI (Magnetic Responance imaging) |  | 48 weeks | 
| Change from the baseline of CMRglc (cerebral metabolic rate for glucose ) analyzed with SPM (statistical parametric mapping) with Brain FDG PET imaging |  | 48 weeks | 
| Changes from the baseline of Amyloid amount analyzed with SPM (statistical parametric mapping) with amyloid PET imaging |  | 48 weeks | 
| Changes of band power in qEEG (Quantitative electroencephalography) |  | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Alzheimer's disease, Mesenchymal Stem cells