The Safety and The Efficacy Evaluation of ET-STEM in Patients With Frontotemporal Dementia

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the safety and the tolerability of 3 repeated doses of ET-STEM (Mesenchymal stem cells preconditioned with ethionamide) in patients with FTD.

Detailed Description
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Subjects with FTD, who signed the informed consent form and meet the eligibility criteria will undergo Ommaya reservoir insertion. 2 weeks after Ommaya reservoir insertion, the subjects will be injected with 3x10^7 cells/2mL of ET-STEM to intraventricular space via an Ommaya reservoir. The injection will be repeated 3 times at 4 week intervals. The subjects will be hospitalized for 24 hours and observed for acute adverse events. 4 weeks after the 3rd injection, safety and potential efficacy will be assessed.

Official Title
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Clinical Assessment on the Safety and Potential Efficacy of Mesenchymal Stem Cells Preconditioned With Ethionamide (ET-STEM) in Patients With Frontotemporal Dementia (FTD)

Conditions
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Frontotemporal Dementia

Intervention / Treatment
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* Drug: ET-STEM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Korean male or female at 40-85 years of age Diagnosis of one of the 3 subtyes of FTD according to the diagnostic criteria for 3 subtypes of FTD ① Probable bvFTD (behavior variant FTD) ② svPPA (semantic variant primary progressive aphasia) ③ nfvPPA (nonfluent/agrammatic variant primary progressive aphasia) K-MMSE ≥ 10 Subjects with trusted caregivers who regularly contact the subjects and can accompany the subjects when visiting the hospital. Negative result of amyloid PET imaging 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: Subjects with dementia cause by other than FTD (i.e. infection of central nervous system, Creutzfeld-Jacob disease, severer head trauma, Huntington's disease, Parkinson's disease, Alzheimer's disease and vascular dementia) Subjects with psychological disorder. (i.e. depression, schizophrenia , bipolar disorder, etc) (except for subjects who were misdiagnosed with psychological disease due to the initial neuropsychiatric symptoms of FTD) Subjects with uncontrolled hypotension, hypertension, diabetes and thyroid disease. Subjects with a cancer (including brain tumor) Subjects with bleeding disorder Woman of childbearing age who refused to practice medically acceptable contraceptive method (post menopausal patient with no menstruation for at least 12 months is considered as infertile) Pregnant or lactating females History of stroke within 3 months prior to study enrollment Substance/alcohol abuse 1 Contraindicated for any of the tests performed during the clinical trial period(for example, MRI, CT,PET) A subject in whom Ommaya reservoir insertion and general anesthesia are considered difficult Abnormal Laboratory findings at Screening Suspected active lung disease based on chest X-ray at Screening Positive hepatitis B nuclear antibody and hpatitis C antibody Subjects who the principal investigator considers inappropriate for participation in the study due to the possible harmful effect on the subjects,difficulty in study completion, or previous or current medical conditions that may disturb evaluation of study results Subjects who the principal investigator considers impossible to comply with clinical research procedures.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single Group
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>injected with 3x10^7 cells/2mL of ET-STEM to intraventricular space via an Ommaya reservoir. repeated 3 times at 4 week intervals | Drug: ET-STEM<br>* mesenchymal stem cells preconditioned with ethionamide<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine DLT (Dose limiting toxicity) | incidence rate of DLT (Dose limiting toxicity) | First 3-week cycle of treatment | 
| adverse events as assessed by CTCAE v5.0 | all potentially treated subjects to assess the safety | up to 5years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADAS-Cog 13 response rate | response rate, no change or improvement on ADAS cog 13 score | Screening, after the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| The Clinical Dementia Rating Sum of Boxes | Change from the baseline in CDR-SB, min 0, max 24, higher scores mean a worse outcome | Screening, after the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| Alzheimer's Disease Cooperative Study- instrumental items of the Activities of Daily Living Inventory | Change from the baseline in ADCS-iADL, min 0, max78, higher scores mean a better outcome | the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| Caregiver-administered Neuropsychiatric Inventory | Change from the baseline in CGA-NPI, min 0, max 144, higher scores mean a worse outcome | the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks | 
| preliminary efficacy | Change from the baseline in CSF biomarkers | up to 12weeks | 
| K-MMSE | Korean Mini-Mental State Examination(MMSE), min 0, max 30, higher scores mean a better outcome | the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks |