Clinical trial NCT02054208: Safety and Exploratory Efficacy Study of NEUROSTEM® Versus Placebo in Patients With Alzheimer's Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Alzheimer's Disease
Keywords: human umbilical cord blood derived mesenchymal stem cells
stem cells
alzheimer's disease
cognitive ability
mesenchymal stem cells
cord blood
Lead sponsor: Medipost Co Ltd.
Sponsor class: INDUSTRY
First posted: 2014-02-04
Enrollment: 46
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of subjects with adverse events
timeFrame: 24 weeks after the first dose
Secondary outcomes:
measure: Change from the baseline in ADAS-Cog
timeFrame: 24 weeks after the first dose
measure: Change from the baseline in S-IADL
timeFrame: 24 weeks after the first dose
measure: Change from the baseline in K-MMSE
timeFrame: 24 weeks after the first dose
measure: Change from the baseline in CGA-NPI
timeFrame: 24 weeks from the first dose
measure: ADAS-Cog Response Rate
timeFrame: 24 weeks after the first dose
measure: Change in CDR-SOB
timeFrame: 24 weeks after the first dose
measure: Change in Florbetaben-PET
timeFrame: 24 weeks after the first dose
measure: Change in FDG-PET (CMRglc: regional cerebral metabolic rate for glucose)
timeFrame: 24 weeks after the first dose
measure: Change in CIBIC-plus
timeFrame: 24 weeks after the first dose
measure: Change from baseline in MRI (DTI mapping)
timeFrame: 24 weeks after the first dose
measure: Change from the baseline in CSF biomarkers
timeFrame: 24 weeks after the first dose
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
affiliation: Medipost Co Ltd.
name: Wonil Oh, MD, PhD
role: STUDY_DIRECTOR
References:
citation: 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.