Clinical trial NCT05315661: The Safety and The Efficacy Evaluation of ET-STEM in Patients With Frontotemporal Dementia
Official title: Clinical Assessment on the Safety and Potential Efficacy of Mesenchymal Stem Cells Preconditioned With Ethionamide (ET-STEM) in Patients With Frontotemporal Dementia (FTD)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Frontotemporal Dementia
Lead sponsor: Samsung Medical Center
Sponsor class: OTHER
First posted: 2022-04-07
Enrollment: 12
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Group
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Korean male or female at 40-85 years of age
2. 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)
3. K-MMSE ≥ 10
4. Subjects with trusted caregivers who regularly contact the subjects and can accompany the subjects when visiting the hospital.
5. Negative result of amyloid PET imaging
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. 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)
2. 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)
3. Subjects with uncontrolled hypotension, hypertension, diabetes and thyroid disease.
4. Subjects with a cancer (including brain tumor)
5. Subjects with bleeding disorder
6. 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)
7. Pregnant or lactating females
8. History of stroke within 3 months prior to study enrollment
9. Substance/alcohol abuse 1
10. Contraindicated for any of the tests performed during the clinical trial period(for example, MRI, CT,PET)
11. A subject in whom Ommaya reservoir insertion and general anesthesia are considered difficult
12. Abnormal Laboratory findings at Screening
13. Suspected active lung disease based on chest X-ray at Screening
14. Positive hepatitis B nuclear antibody and hpatitis C antibody
15. 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
16. Subjects who the principal investigator considers impossible to comply with clinical research procedures.

Primary outcomes:
measure: To determine DLT (Dose limiting toxicity)
timeFrame: First 3-week cycle of treatment
measure: adverse events as assessed by CTCAE v5.0
timeFrame: up to 5years
Secondary outcomes:
measure: ADAS-Cog 13 response rate
timeFrame: Screening, after the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: The Clinical Dementia Rating Sum of Boxes
timeFrame: Screening, after the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: Alzheimer's Disease Cooperative Study- instrumental items of the Activities of Daily Living Inventory
timeFrame: the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: Caregiver-administered Neuropsychiatric Inventory
timeFrame: the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
measure: preliminary efficacy
timeFrame: up to 12weeks
measure: K-MMSE
timeFrame: the first administration12weeks, 48weeks, 96weeks, 144weeks, 192weeks, 240weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
state: Gangnam-gu
Study officials:
affiliation: Samsung Medical Center
name: HeeJin Kim
role: PRINCIPAL_INVESTIGATOR
References: