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

• ClinicalTrials.gov Identifier: NCT02054208
• Recruitment Status: Completed
• First Posted: February 4, 2014
• Last Update Posted: August 28, 2020
• Sponsor: Medipost Co Ltd.
• Information provided by (Responsible Party): Medipost Co Ltd.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alzheimer's Disease	Biological: human umbilical cord blood derived mesenchymal stem cells; Other: Normal saline 2mL	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 46 participants
• 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
• 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
• Actual Study Start Date: March 2014
• Actual Primary Completion Date: December 2019
• Actual Study Completion Date: December 2019

Arms and Interventions

Arm	Intervention/treatment
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	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
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	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
Placebo Comparator: Placebo; normal saline 2mL, doses separated by 4 weeks for a total of 3 doses	Other: Normal saline 2mL; Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations

Outcome Measures

Primary Outcome Measures :

1. 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

Secondary Outcome Measures :

1. Change from the baseline in ADAS-Cog [ Time Frame: 24 weeks after the first dose ]
   Alzheimer's Disease assessment Scale-Cognitive Subscale
2. Change from the baseline in S-IADL [ Time Frame: 24 weeks after the first dose ]
   Seoul Instrumental Activities of Daily Living
3. Change from the baseline in K-MMSE [ Time Frame: 24 weeks after the first dose ]
   Mini Mental State Exmination Korean version
4. Change from the baseline in CGA-NPI [ Time Frame: 24 weeks from the first dose ]
   Caregiver-administered Neuropsychiatric Inventory
5. 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
6. Change in CDR-SOB [ Time Frame: 24 weeks after the first dose ]
   Clinical Dementia Rating-Sum of Box
7. Change in Florbetaben-PET [ Time Frame: 24 weeks after the first dose ]
   Florbetaben - Pittsburgh Compound B-positron emission tomography
8. Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose) [ Time Frame: 24 weeks after the first dose ]
   fluorodeoxyglucose positron emission tomography
9. Change in CIBIC-plus [ Time Frame: 24 weeks after the first dose ]
   The Clinician's Interview Based Impression of Change-plus
10. Change from baseline in MRI (DTI mapping) [ Time Frame: 24 weeks after the first dose ]
    MRI Analysis
11. Change from the baseline in CSF biomarkers [ Time Frame: 24 weeks after the first dose ]
    biomakrer analysis

Eligibility Criteria

• Ages Eligible for Study: 50 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Korea, Republic of

Samsung Medical Center

Seoul, Korea, Republic of

Sponsors and Collaborators

Medipost Co Ltd.

Investigators

• Study Director: Wonil Oh, MD, PhD; Medipost Co Ltd.

More Information

Additional Information:

first-in-man study of NEUROSTEM 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kim HJ, Cho KR, Jang H, Lee NK, Jung YH, Kim JP, Lee JI, Chang JW, Park S, Kim ST, Moon SW, Seo SW, Choi SJ, Na DL. Intracerebroventricular injection of human umbilical cord blood mesenchymal stem cells in patients with Alzheimer's disease dementia: a phase I clinical trial. Alzheimers Res Ther. 2021 Sep 14;13(1):154. doi: 10.1186/s13195-021-00897-2.

• Responsible Party: Medipost Co Ltd.
• ClinicalTrials.gov Identifier: NCT02054208
• Other Study ID Numbers: MP-CR-010
• First Posted: February 4, 2014
• Last Update Posted: August 28, 2020
• Last Verified: August 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

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