Open-label, Dose-escalation, Phase 1 Clinical Trial to Determine the Safety and Dose of EN001 in Patients with Duchenne Muscular Dystrophy(DMD)
It is the first in human (FIH), 3+3 design clinical trial to evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of EN001 (allogeneic umbilical cord-derived mesenchymal stem cells) in the treatment of Duchenne Muscular Dystrophy (DMD).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
7
EN001 intravenously (IV) in the treatment of Duchenne Muscular Dystrophy (DMD) Dosage for each group is as follows. Dose group A (Low dose): 5.0x10\^5 cells/kg
EN001 intravenously (IV) in the treatment of Duchenne Muscular Dystrophy (DMD) Dosage for each group is as follows. Dose group B (High dose): 2.5x10\^6 cells/kg
Samsung Medical Center
Seoul, South Korea
Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time frame: Week 12 after treatment
Determination of Dose-limiting toxicity (DLT) levels of EN001
Among the adverse events occurring for 2 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE 5.0
Time frame: Up to Week 2 after dosing on Day 0
Determination of Maximum tolerated dose (MTD) levels of EN001
Among the adverse events occurring for 2 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE 5.0 Maximum tolerated dose defines the evaluated maximum dose level in which greater than two participants of six participants experience Dose-limiting toxicity (DLT) under the dose level. The dose level where two participants of six participants experience DLT will be the maximum tolerated dose.
Time frame: Up to Week 2 after dosing on Day 0
Number of participants with Vital Signs abnormalities
Vital Signs include blood pressure (mmHg), pulse (times/minute), respiratory rate (times/minute), and body temperature (℃) and will be assessed by CTCAE v 5.0 to evaluate safety and tolerability of EN001. The number of participants with at least one potentially clinically significant abnormal vital sign finding were reported as treatment emergent adverse events (TEAEs).
Time frame: Week 12 after screening
Number of participants with clinically significant abnormalities of Physical Examinations
Physical Examinations include general appearance, head, ears/eyes/nose/throat, cardiovascular, respiratory, abdomen, skin, lymph nodes, extremities, musculoskeletal and neurologic and will be assessed by CTCAE v 5.0 to evaluate safety and tolerability of EN001. Number of participants with potentially clinically significant abnormalities in physical examinations were reported as TEAEs.
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Time frame: From screening up to Week 12
Number of participants with abnormalities of Laboratory Parameters
Laboratory Parameters include hematology, chemistry laboratory tests, urinalysis, coagulation test and plasma viral load test and will be assessed by CTCAE 5.0 to evaluate safety and tolerability of EN001. Number of participants with at least one potentially clinically significant abnormal finding were reported as TEAEs.
Time frame: From screening up to Week 12
Number of participants with abnormalities of 12-lead Electrocardiography (ECG)
Categorical summarization ECG criteria were as follows: 1. QT interval, QTcB, QTcF and QTcP: increase from baseline \>30 millisecond \[ms\] or 60 ms; absolute value \> 450 ms, \>480 ms, and \> 500 ms; 2. heart rate (HR): change from baseline ≥20 beats per minute \[bpm\] and absolute value≤50 bpm or ≥120 bpm; 3. PR interval: absolute value ≥220 ms and increase from baseline≥20 ms; 4. QRS: ≥120 ms.
Time frame: From screening to baseline on Day 0 (Predose to end of infusion and 90 min after completion of infusion)
Incidence of adverse events (AEs)
Occurrence of any adverse reactions, development of new blood clots, tumors, immune responses (like autoimmune reactions) and death, and/or serious adverse events related investigational product will be summarized by actual treatment groups respectively.
Time frame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject)
Number of participants with abnormalities of Vital Signs, Physical Findings, and Laboratory Parameters
Abnormalities of Vital Signs, Physical Findings, and Laboratory parameters (as described above) will be collected and analyzed, and then assessed by CTCAE 5.0 to evaluate the long-term safety of EN001.
Time frame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject)
Rate of change at the time of visit compared to baseline (percent [%]) in CK level
Creatinine kinase (CK) level will be collected and analyzed to evaluate the exploratory efficacy of EN001. \- CK level(%) = (CK level after dosing - CK level in baseline)/(CK level in baseline)\*100
Time frame: From screening up to the end of support (up to approximately 5 years per subject at each visit)
Change from baseline in Function tests
Function tests measured by North Star Ambulatory Assessment (NSAA), Six Minute Walk Test (6MWT), Myometry. and Lung capacity (and only K-Cross Motor Function Measure (KGMFM) will be performed under 5 years old) will be collected and analyzed to evaluate the exploratory efficacy of EN001. \- Function tests = value in visit - value in baseline
Time frame: Screening and baseline on Day -1 (up to approximately 5 years per subject after Week 12)