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

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2016 by Medipost Co Ltd.
Sponsor:
Information provided by (Responsible Party):
Medipost Co Ltd.
ClinicalTrials.gov Identifier:
NCT02054208
First received: January 29, 2014
Last updated: January 6, 2016
Last verified: January 2016
  Purpose
This combined phase 1/2a clinical trial is to investigate the safety, dose limiting toxicity (DLT), and exploratory efficacy of three repeated intraventricular administrations of NEUROSTEM® (human umbilical cord blood-derived mesenchymal stem cells) versus placebo via an Ommaya reservoir at 4 week intervals in patients with Alzheimer's disease.

Condition Intervention Phase
Alzheimer's Disease
Biological: human umbilical cord blood derived mesenchymal stem cells
Procedure: Ommaya reservoir insertion
Other: Normal saline 2mL
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Single-center, Phase 1/2a Clinical Trial to Evaluate the Safety and Exploratory Efficacy of Intraventricular Administrations of NEUROSTEM® Versus Placebo Via an Ommaya Reservoir in Patients With Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Medipost Co Ltd.:

Primary Outcome Measures:
  • Number of subjects with adverse events [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: Yes ]
    Number of subjects with adverse event, number of subjects with normal range of vital signs, mixed lymphocyte reaction result, and laboratory examination result


Secondary Outcome Measures:
  • Change from the baseline in ADAS-Cog [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    Alzheimer's Disease assessment Scale-Cognitive Subscale

  • Change from the baseline in S-IADL [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    Seoul Instrumental Activities of Daily Living

  • Change from the baseline in K-MMSE [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    Mini Mental State Exmination Korean version

  • Change from the baseline in CGA-NPI [ Time Frame: 24 weeks from the first dose ] [ Designated as safety issue: No ]
    Caregiver-administered Neuropsychiatric Inventory

  • ADAS-Cog Response Rate [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    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 CDR-SOB [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    Clinical Dementia Rating-Sum of Box

  • Change in Florbetaben-PET [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    Florbetaben - Pittsburgh Compound B-positron emission tomography

  • Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose) [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    fluorodeoxyglucose positron emission tomography

  • Change in CIBIC-plus [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
    The Clinician's Interview Based Impression of Change-plus

  • Change from baseline in MRI (DTI mapping) [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]
  • Change from the baseline in CSF biomarkers [ Time Frame: 24 weeks after the first dose ] [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: February 2014
Estimated Study Completion Date: February 2018
Estimated Primary Completion Date: February 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: NEUROSTEM (hUCB-MSCs)- low dose
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

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

Other Name: NEUROSTEM
Procedure: Ommaya reservoir insertion
Experimental: NEUROSTEM (hUCB-MSCs) - high dose
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

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

Other Name: NEUROSTEM
Procedure: Ommaya reservoir insertion
Placebo Comparator: Placebo
normal saline 2mL, doses separated by 4 weeks for a total of 3 doses
Procedure: Ommaya reservoir insertion Other: Normal saline 2mL
Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Korean male or female at 50 -85 years of age
  2. Diagnosis of Probable Alzheimer type or mild cognitive impairment due to Alzheimer's disease (stage A) according to NINCDS-ADRDA criteria at Visit 1 (Screening)
  3. Korea Mini-Mental State Examination (KMMSE) score of 18 - 26 at Visit 1 (Screening)
  4. Positive for Amyloid on PIB-PET or Florbetaben PET
  5. A subject with neurodegeneration (mild atrophy of the brain) as confirmed by MRI
  6. 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:

  1. Concurrent mental disorder (such as schizophrenia, depression, bi-polar diseases or others) aside from dementia
  2. 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
  3. 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
  4. History of stroke within 3 months prior to study enrollment
  5. Severe liver disorder (equivalent to double the normal values of ALT and AST) at Visit 1
  6. Severe kidney disorder (serum creatinine ≥1.5mg/dL) at Visit 1
  7. Pregnant or lactating females
  8. 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
  9. Suspected active lung disease based on chest X-ray at Visit 1
  10. 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)
  11. History of screening failure for the clinical trial of NEUROSTEM® in the past 6 months
  12. Participation in another clinical trial in the past 3 months prior to the beginning (Week 0) of this clinical trial
  13. 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)
  14. Diagnosis of cancer (of any body system, including brain tumor
  15. Substance/alcohol abuse
  16. Contraindicated for any of the tests performed during the clinical trial period (for example, MRI, CT, PET)
  17. A subject in whom Ommaya reservoir insertion is considered difficult
  18. Whom the principal investigator considers inappropriate for participation in the study due to any reasons other than those listed above
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02054208

Contacts
Contact: Wonil Oh, MD +82-2-3465-6670 wioh@medi-post.co.kr

Locations
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Yunkyung Choi, MD    82-2-3410-6486    yk221.choi@samsung.com   
Principal Investigator: Duk L. Na, MD         
Sponsors and Collaborators
Medipost Co Ltd.
Investigators
Study Director: Wonil Oh, MD, PhD Medipost Co Ltd.
  More Information

Additional Information:
Responsible Party: Medipost Co Ltd.
ClinicalTrials.gov Identifier: NCT02054208     History of Changes
Other Study ID Numbers: MP-CR-010 
Study First Received: January 29, 2014
Last Updated: January 6, 2016
Health Authority: Korea: Ministry of Food and Drug Safety

Keywords provided by Medipost Co Ltd.:
human umbilical cord blood derived mesenchymal stem cells
stem cells
alzheimer's disease
cognitive ability
mesenchymal stem cells
cord blood

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders

ClinicalTrials.gov processed this record on September 27, 2016