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

Alzheimer's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02054208
• Other study ID #: MP-CR-010
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: March 2014
• Est. completion date: December 2019

Study information

• Verified date: August 2018
• Source: Medipost Co Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 46
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease

Intervention

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:
• Normal saline 2mL
Intraventricular administrations of 2mL Normal Saline at 4 week intervals via an Ommaya Reservoir, for a total of 3 administrations

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
Medipost Co Ltd.

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events	Number of subjects with adverse event, number of subjects with normal range of vital signs, mixed lymphocyte reaction result, and laboratory examination result	24 weeks after the first dose
Secondary	Change from the baseline in ADAS-Cog	Alzheimer's Disease assessment Scale-Cognitive Subscale	24 weeks after the first dose
Secondary	Change from the baseline in S-IADL	Seoul Instrumental Activities of Daily Living	24 weeks after the first dose
Secondary	Change from the baseline in K-MMSE	Mini Mental State Exmination Korean version	24 weeks after the first dose
Secondary	Change from the baseline in CGA-NPI	Caregiver-administered Neuropsychiatric Inventory	24 weeks from the first dose
Secondary	ADAS-Cog Response Rate	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	24 weeks after the first dose
Secondary	Change in CDR-SOB	Clinical Dementia Rating-Sum of Box	24 weeks after the first dose
Secondary	Change in Florbetaben-PET	Florbetaben - Pittsburgh Compound B-positron emission tomography	24 weeks after the first dose
Secondary	Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose)	fluorodeoxyglucose positron emission tomography	24 weeks after the first dose
Secondary	Change in CIBIC-plus	The Clinician's Interview Based Impression of Change-plus	24 weeks after the first dose
Secondary	Change from baseline in MRI (DTI mapping)	MRI Analysis	24 weeks after the first dose
Secondary	Change from the baseline in CSF biomarkers	biomakrer analysis	24 weeks after the first dose

External Links

•   first-in-man study of NEUROSTEM