To evaluate the safety and tolerability of allogeneic bone marrow-derived mesenchymal stem cells (CE211NS21) in patients with severe anti-aquaporin-4-immunoglobulin G positive neuromyelitis optica spectrum disorder (AQP4-IgG-positive NMOSD) relapse
CE211NS21 is an allogeneic myeloid-derived mesenchymal stem cell therapy that secretes various growth factors and cytokines and regulates immune activity to rejuvenate myelin, and this clinical trial aims to confirm the safety and tolerability of CE211NS21 in phase 1 clinical trials in patients with anti-aquaporin4 antibody-positive optic spectrum category disease. In terms of risk assessment, the safety was confirmed when 1x10\^6 cells/kg of CE211NS21 was administered to C57BL6 mice three times at intervals of two weeks, and safety and tolerability were confirmed when 1x10\^6 cells/kg of allogeneic myeloid-derived mesenchymal stem cells (CS20BR08) were administered in the intrathecal twice at 28 days intervals in therapeutic use in NMOSD patients. When CE211NS21 was administered to C57BL6 mice intrathecal, the lethal dose exceeded the high dose of 1x10\^6 cells/kg, and the non-toxic dose (NOAEL) was 1x10\^6 cells/head/20uL when administered repeatedly three times at intervals of two weeks into the intrathecal. Therefore, in this clinical trial, CE211NS21 (step 1 dose 1.0x10\^6 cells/kg, step 2x10\^6 cells/kg) was set to be administered three times in consideration of the toxicity test result of three repeated doses and the safety of up to three doses in therapeutic clinical trials. And the administration administers the first or second-stage dose into the intrathecal at baseline, at 4 weeks and at 16 weeks.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
6
baseline (D0), 4-week point (Visit 3), and 16-week point (Visit 6) for intrathecal administration of CE211NS21, Step 1 dose : 1x10\^6 cells/kg Step 2 dose : 2x10\^6 cells/kg; The Duration of follow up study following the administration of CE211NS21 is 5 years
Dose-Limiting Toxicity
To evaluate the incidence of dose-limiting toxicity (DLT) of CE211NS21 Injection in patients with NMOSD relapse.
Time frame: [Time Frame: up to 4 weeks]
Adverse Events (AEs)
To evaluate the safety and tolerability of CE211NS21 Injection in patients with NMOSD relapse by assessing treatment-emergent adverse events.
Time frame: [Time Frame: up to 4 weeks]
Functional System Score
To evaluate functional impairment in patients with NMOSD relapse using the Functional System Score.
Time frame: 12 weeks, 24 weeks
36-item Short Form Survey (SF-36)
To evaluate health-related quality of life in patients with NMOSD relapse using SF-36.
Time frame: [Time Frame: 12 weeks, 24 weeks]
Expanded Disability Status Scale (EDSS)
To measure disability level in patients with NMOSD relapse using EDSS.
Time frame: [Time Frame: 12 weeks, 24 weeks]
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