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

Phase 1

Completed

• Conditions: Alzheimer's Disease
• Interventions: Biological: human umbilical cord blood derived mesenchymal stem cells; Other: Normal saline 2mL

• Registration Number: NCT02054208
• Lead Sponsor: Medipost Co Ltd.

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 Timeline

• Study First Submitted: 2014-01-29
• Study First Submitted QC: 2014-02-03
• Study First Posted: 2014-02-04
• Study Start: 2014-03
• Status Verified: 2018-08
• Primary Completion: 2019-12
• Study Completion: 2019-12
• Last Update Submitted: 2020-08-26
• Last Update Posted: 2020-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 46

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NEUROSTEM (hUCB-MSCs)- low dose	human umbilical cord blood derived mesenchymal stem cells	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
NEUROSTEM (hUCB-MSCs) - high dose	human umbilical cord blood derived mesenchymal stem cells	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
Placebo	Normal saline 2mL	normal saline 2mL, doses separated by 4 weeks for a total of 3 doses

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events	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

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

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Korea, Republic of