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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Frontotemporal Dementia
• Intervention / Treatment: Drug: ET-STEM

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 Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Gangnam-gu
    • Seoul, Gangnam-gu, Korea, Republic of, 06351
      • Samsung Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; 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; mesenchymal stem cells preconditioned with ethionamide

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Samsung Medical Center
• Investigators: Principal Investigator: HeeJin Kim, Samsung Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: March 1, 2022
• First Submitted That Met QC Criteria: March 30, 2022
• First Posted (Actual): April 7, 2022

Study Record Updates

• Last Update Posted (Estimated): February 21, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Dementia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: 2022-02-089

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No