This is a open-label, single-arm, dose escalation phase I clinical trial. The goal of this clinical trial is to evaluate the safety and preliminary efficacy of Intrathecal injection human umbilical cord-derived mesenchymal stromal cell-derived extracellular vesicle (hUC-MSC-sEV) in syringomyelia.
This is a open-label, single-arm, dose escalation phase I clinical trial. The study will consist of one part: Part 1 will be a dose-escalation study. A traditional 3+3 dose-escalation design will be implemented in Part 1. Cohort 1 will receive low-dose1×1011particles; Cohort 2 will receive middle-dose2×1011particles; and Cohort 3 will receive high-dose3×1011particles. (Cohort 1 to Cohort 3 will receive a dose of 2 ml per lumbar puncture, administered once a month, for a total of three months.) If no dose-limiting toxicities (DLTs) are observed for 2 weeks after the administration of the first Intrathecal injection, a new cohort will be enrolled at the next planned dose level. If DLTs are observed in one participant in the cohort, an additional three participants will be treated at the same dose level. Dose escalation will be stopped if DLTs are observed in more than 33% of the participants.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Exosomes derived from human umbilical cord blood mesenchymal stem cells for Intrathecal injection (administered once a month, for a total of three months, based on the recommended dose during the dose-escalation phase).
Xuanwu Hospital
Beijing, Beijing City, China
RECRUITINGNumber of participants who experienced dose-limiting Toxicities (DLTs)
DLTs related to hUC-MSC-sEV include adverse events of grade 3 or higher (including significant clinical laboratory findings) that are possibly, likely, or definitely related to the study drug, accompanied by clinical symptoms and requiring medical treatment within 14 days of administration. Adverse events are graded according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0).
Time frame: 24 hours, 4±1 Weeks, 8±1 Weeks,12±1 Weeks
American Spinal Injury Association(ASIA) Score
American Spinal Injury Association(ASIA) Score for evaluating the spinal cord function, degree of the spinal cord function, motor1-100, sensory 1-224, higher scores mean a better outcome
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
Klekamp and Sammi syringomyelia scale
for evaluating the spinal cord function, each score 1-5, higher scores mean a better outcome
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
Incidence of severe adverse events
The proportion of patients who experienced severe adverse events.
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks
Time to event (death, tracheostomy, and permanent assisted mechanical ventilation)
The number of time-to-event outcomes.
Time frame: up to 12 months
modified Japanese Orthopaedic Association Scores (mJOA)
Motor function, sensory, bladder function;for evaluating the spinal cord function;0-17, higher scores mean a better outcome
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
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xuanwu syringomyelia scale
for evaluating the spinal cord function, for evaluating the spinal cord function;0-18, higher scores mean a worse outcome
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months
improvement or resolution of the syrinx
improvement in size.
Time frame: 4±1 Weeks, 8±1 Weeks,12±1 Weeks, 12±1 months