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

Phase 1

Active, not recruiting

• Conditions: Frontotemporal Dementia
• Interventions: Drug: ET-STEM

• Registration Number: NCT05315661
• Lead Sponsor: Samsung Medical Center

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.

Study Timeline

• Study First Submitted: 2022-03-01
• Study First Submitted QC: 2022-03-30
• Study First Posted: 2022-04-07
• Study Start: 2022-07-06
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-20
• Last Update Posted: 2024-02-21
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 12

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	ET-STEM	injected with 3x10\^7 cells/2mL of ET-STEM to intraventricular space via an Ommaya reservoir. repeated 3 times at 4 week intervals

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Samsung Medical Center; 🇰🇷 Seoul, Gangnam-gu, Korea, Republic of