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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02054208
Recruitment Status : Completed
First Posted : February 4, 2014
Last Update Posted : August 28, 2020
Sponsor:
Information provided by (Responsible Party):
Medipost Co Ltd.

Tracking Information
First Submitted Date  ICMJE January 29, 2014
First Posted Date  ICMJE February 4, 2014
Last Update Posted Date August 28, 2020
Actual Study Start Date  ICMJE March 2014
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2014)
Number of subjects with adverse events [ Time Frame: 24 weeks after the first dose ]
Number of subjects with adverse event, number of subjects with normal range of vital signs, mixed lymphocyte reaction result, and laboratory examination result
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
  • Change from the baseline in ADAS-Cog [ Time Frame: 24 weeks after the first dose ]
    Alzheimer's Disease assessment Scale-Cognitive Subscale
  • Change from the baseline in S-IADL [ Time Frame: 24 weeks after the first dose ]
    Seoul Instrumental Activities of Daily Living
  • Change from the baseline in K-MMSE [ Time Frame: 24 weeks after the first dose ]
    Mini Mental State Exmination Korean version
  • Change from the baseline in CGA-NPI [ Time Frame: 24 weeks from the first dose ]
    Caregiver-administered Neuropsychiatric Inventory
  • ADAS-Cog Response Rate [ Time Frame: 24 weeks after the first dose ]
    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 ]
    Clinical Dementia Rating-Sum of Box
  • Change in Florbetaben-PET [ Time Frame: 24 weeks after the first dose ]
    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 ]
    fluorodeoxyglucose positron emission tomography
  • Change in CIBIC-plus [ Time Frame: 24 weeks after the first dose ]
    The Clinician's Interview Based Impression of Change-plus
  • Change from baseline in MRI (DTI mapping) [ Time Frame: 24 weeks after the first dose ]
    MRI Analysis
  • Change from the baseline in CSF biomarkers [ Time Frame: 24 weeks after the first dose ]
    biomakrer analysis
Original Secondary Outcome Measures  ICMJE
 (submitted: February 3, 2014)
  • Change from the baseline in S-IADL [ Time Frame: 24 weeks after the first dose ]
    Seoul Instrumental Activities of Daily Living
  • Change from the baseline in K-MMSE [ Time Frame: 24 weeks after the first dose ]
    Mini Mental State Exmination Korean version
  • Change from the baseline in CGA-NPI [ Time Frame: 24 weeks from the first dose ]
    Caregiver-administered Neuropsychiatric Inventory
  • ADAS-Cog Response Rate [ Time Frame: 24 weeks after the first dose ]
    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 PIB-PET (SUV: Standard uptake values) [ Time Frame: 24 weeks after the first dose ]
    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 ]
    fluorodeoxyglucose positron emission tomography
  • Change in CIBIC-plus [ Time Frame: 24 weeks after the first dose ]
    The Clinician's Interview Based Impression of Change-plus
  • Change Change from baseline in MRI (DTI mapping) [ Time Frame: 24 weeks after the first dose ]
  • Change from the baseline in CSF biomarkers [ Time Frame: 24 weeks after the first dose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Safety and Exploratory Efficacy Study of NEUROSTEM® Versus Placebo in Patients With Alzheimer's Disease
Official Title  ICMJE 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
Brief Summary 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.
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Stage 1: 9 subjects (3 subjects for low dose and 6 subjects for high dose) Stage 2: 36 subjects ( 24 subjects for high dose and 12 subjects for placebo) A total of 45 subjects to be enrolled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Alzheimer's Disease
Intervention  ICMJE
  • 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
  • Other: Normal saline 2mL
    Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations
Study Arms  ICMJE
  • Experimental: NEUROSTEM (hUCB-MSCs)- low dose
    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
    Intervention: Biological: human umbilical cord blood derived mesenchymal stem cells
  • Experimental: NEUROSTEM (hUCB-MSCs) - high dose
    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
    Intervention: Biological: human umbilical cord blood derived mesenchymal stem cells
  • Placebo Comparator: Placebo
    normal saline 2mL, doses separated by 4 weeks for a total of 3 doses
    Intervention: Other: Normal saline 2mL
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 26, 2020)
46
Original Estimated Enrollment  ICMJE
 (submitted: February 3, 2014)
40
Actual Study Completion Date  ICMJE December 2019
Actual Primary Completion Date December 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

1 stage Inclusion Criteria:

  1. Korean male or female at 50 -85 years of age
  2. Diagnosis of Probable Alzheimer type 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 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:

  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 NIA-AA criteria at Visit 1(Screening)
  3. Korea Mini-Mental State Examination (KMMSE) score of over 18 at Visit 1 (Screening)
  4. Positive for Amyloid on 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years to 85 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Korea, Republic of
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02054208
Other Study ID Numbers  ICMJE MP-CR-010
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Medipost Co Ltd.
Study Sponsor  ICMJE Medipost Co Ltd.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Wonil Oh, MD, PhD Medipost Co Ltd.
PRS Account Medipost Co Ltd.
Verification Date August 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP