Back to resultsDetermine the Safety and Dose of EN001 in Patients With Duchenne Muscular Dystrophy(DMD)
Primary Purpose
Duchenne Muscular Dystrophy
Status
Completed
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
EN001
EN001
Sponsored by
About this trial
This is an interventional treatment trial for Duchenne Muscular Dystrophy
Eligibility Criteria
Inclusion Criteria:
- Those aged 2 to 18 years old
- Male
- Those who are diagnosed with DMD due to a mutation in the dystrophin gene identified by a genetic test
Phenotypic evidence of DMD
- Clinical signs or symptoms (proximal weakness, waddling gait, Gowers maneuver)
- Elevated serum creatine kinase level
- Those who have been using systemic corticosteroids at a stable dose for 24 weeks prior to screening and are expected to maintain the constant dose throughout the study period
- Those who agree to use effective contraceptive measures until the short-term follow-up period of the clinical trial. In addition, their partner must also use a medically acceptable method of contraception (ie, oral contraceptives for women) for the same period.
- Those who are willing to agree with the ICF and whose parent or representative is willing to provide written consent for the subject's participation in the clinical trial
Exclusion Criteria:
- Those who have clinical signs or symptoms of cardiomyopathy, defined as LVEF <50% on echocardiography at screening
- If ventilatory support is required during the day or if invasive mechanical ventilation via tracheostomy is used (Non-invasive ventilation such as positive pressure ventilation is allowed at night)
- If hepatitis B core antibody and hepatitis C antibody are positive
- If there is a history of major surgery within 12 weeks or it is expected during the study period
- Those who have been exposed to gene therapy or genome editing within 24 weeks from the screening
- Those who have experience with stem cell therapy
- Those who have been administered Translarna granules (Ataluren) within 24 weeks from the screening
- Those who are receiving treatment (other than corticosteroids) that may affect muscle strength or function within 12 weeks prior to screening
If laboratory test values are abnormal at the time of screening
- Hemoglobin <10 g/dL
- Serum albumin <2.5 g/dL
- Platelet count <50,000/ml
- Abnormal GGT or total bilirubin (>laboratory's upper limit of normal)
- Abnormal renal function (Serum creatinine >1.5 Times laboratory's upper limit of normal)"
- Those with significant neuromuscular or genetic diseases other than DMD
- Those with significant heart, lung, liver, kidney, hematological, immunological, behavioral disease, or other clinically significant diseases including malignant tumors
- Those who have a previous or current medical condition that may adversely affect the safety of the subject, make it difficult to complete treatment, or affect the evaluation of clinical trial results at the discretion of the investigator
- Those who do not have the will or ability to comply with clinical trial procedures at the discretion of the investigator
Sites / Locations
- Samsung Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
Dose group A (Low dose)
Dose group B (High dose)
Arm Description
Participants will receive EN001 intravenously (IV) once on Day 1. Before 30 minutes EN001 dosing, there will be premedication (solu-cortef 1-2 mg/kg + Lorazepam 0.1 mg/kg (max 2 mg) + Ondansetron (5 mg/m^2) + Chlorpheniramine (1 mg for 2~6 years old; 2 mg for 6~12 years old; 4 mg for over 12 years old)+ Acetaminophen) administered to assure safety of participants from issues such as immune rejection, due to the process of thawing in a frozen state of EN001.
Participants will receive EN001 intravenously (IV) once on Day 1. Before 30 minutes EN001 dosing, there will be premedication (solu-cortef 1-2 mg/kg + Lorazepam 0.1 mg/kg (max 2 mg) + Ondansetron (5 mg/m^2) + Chlorpheniramine (1 mg for 2~6 years old; 2 mg for 6~12 years old; 4 mg for over 12 years old)+ Acetaminophen) administered to assure safety of participants from issues such as immune rejection, due to the process of thawing in a frozen state of EN001.
Outcomes
Primary Outcome Measures
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
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
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.
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).
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.
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.
Number of participants with abnormalities of 12-lead Electrocardiography (ECG)
Categorical summarization ECG criteria were as follows:
QT interval, QTcB, QTcF and QTcP: increase from baseline >30 millisecond [ms] or 60 ms; absolute value > 450 ms, >480 ms, and > 500 ms;
heart rate (HR): change from baseline ≥20 beats per minute [bpm] and absolute value≤50 bpm or ≥120 bpm;
PR interval: absolute value ≥220 ms and increase from baseline≥20 ms;
QRS: ≥120 ms.
Secondary Outcome Measures
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.
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.
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05338099
Brief Title
Determine the Safety and Dose of EN001 in Patients With Duchenne Muscular Dystrophy(DMD)
Official Title
Open-label, Dose-escalation, Phase 1 Clinical Trial to Determine the Safety and Dose of EN001 in Patients With Duchenne Muscular Dystrophy(DMD)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
January 18, 2022 (Actual)
Primary Completion Date
December 28, 2022 (Actual)
Study Completion Date
December 28, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ENCell
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Open-label, Dose-escalation, Phase 1 Clinical Trial to Determine the Safety and Dose of EN001 in Patients with Duchenne Muscular Dystrophy(DMD)
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Duchenne Muscular Dystrophy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dose group A (Low dose)
Arm Type
Experimental
Arm Description
Participants will receive EN001 intravenously (IV) once on Day 1. Before 30 minutes EN001 dosing, there will be premedication (solu-cortef 1-2 mg/kg + Lorazepam 0.1 mg/kg (max 2 mg) + Ondansetron (5 mg/m^2) + Chlorpheniramine (1 mg for 2~6 years old; 2 mg for 6~12 years old; 4 mg for over 12 years old)+ Acetaminophen) administered to assure safety of participants from issues such as immune rejection, due to the process of thawing in a frozen state of EN001.
Arm Title
Dose group B (High dose)
Arm Type
Experimental
Arm Description
Participants will receive EN001 intravenously (IV) once on Day 1. Before 30 minutes EN001 dosing, there will be premedication (solu-cortef 1-2 mg/kg + Lorazepam 0.1 mg/kg (max 2 mg) + Ondansetron (5 mg/m^2) + Chlorpheniramine (1 mg for 2~6 years old; 2 mg for 6~12 years old; 4 mg for over 12 years old)+ Acetaminophen) administered to assure safety of participants from issues such as immune rejection, due to the process of thawing in a frozen state of EN001.
Intervention Type
Drug
Intervention Name(s)
EN001
Other Intervention Name(s)
EN001 (allogeneic umbilical cord-derived mesenchymal stem cells)
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
EN001
Other Intervention Name(s)
EN001 (allogeneic umbilical cord-derived mesenchymal stem cells)
Intervention Description
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
Primary Outcome Measure Information:
Title
Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame
Week 12 after treatment
Title
Determination of Dose-limiting toxicity (DLT) levels of EN001
Description
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
Title
Determination of Maximum tolerated dose (MTD) levels of EN001
Description
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
Title
Number of participants with Vital Signs abnormalities
Description
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
Title
Number of participants with clinically significant abnormalities of Physical Examinations
Description
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.
Time Frame
From screening up to Week 12
Title
Number of participants with abnormalities of Laboratory Parameters
Description
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
Title
Number of participants with abnormalities of 12-lead Electrocardiography (ECG)
Description
Categorical summarization ECG criteria were as follows:
QT interval, QTcB, QTcF and QTcP: increase from baseline >30 millisecond [ms] or 60 ms; absolute value > 450 ms, >480 ms, and > 500 ms;
heart rate (HR): change from baseline ≥20 beats per minute [bpm] and absolute value≤50 bpm or ≥120 bpm;
PR interval: absolute value ≥220 ms and increase from baseline≥20 ms;
QRS: ≥120 ms.
Time Frame
From screening to baseline on Day 0 (Predose to end of infusion and 90 min after completion of infusion)
Secondary Outcome Measure Information:
Title
Incidence of adverse events (AEs)
Description
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)
Title
Number of participants with abnormalities of Vital Signs, Physical Findings, and Laboratory Parameters
Description
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)
Title
Rate of change at the time of visit compared to baseline (percent [%]) in CK level
Description
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)
Title
Change from baseline in Function tests
Description
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)
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Those aged 2 to 18 years old
Male
Those who are diagnosed with DMD due to a mutation in the dystrophin gene identified by a genetic test
Phenotypic evidence of DMD
Clinical signs or symptoms (proximal weakness, waddling gait, Gowers maneuver)
Elevated serum creatine kinase level
Those who have been using systemic corticosteroids at a stable dose for 24 weeks prior to screening and are expected to maintain the constant dose throughout the study period
Those who agree to use effective contraceptive measures until the short-term follow-up period of the clinical trial. In addition, their partner must also use a medically acceptable method of contraception (ie, oral contraceptives for women) for the same period.
Those who are willing to agree with the ICF and whose parent or representative is willing to provide written consent for the subject's participation in the clinical trial
Exclusion Criteria:
Those who have clinical signs or symptoms of cardiomyopathy, defined as LVEF <50% on echocardiography at screening
If ventilatory support is required during the day or if invasive mechanical ventilation via tracheostomy is used (Non-invasive ventilation such as positive pressure ventilation is allowed at night)
If hepatitis B core antibody and hepatitis C antibody are positive
If there is a history of major surgery within 12 weeks or it is expected during the study period
Those who have been exposed to gene therapy or genome editing within 24 weeks from the screening
Those who have experience with stem cell therapy
Those who have been administered Translarna granules (Ataluren) within 24 weeks from the screening
Those who are receiving treatment (other than corticosteroids) that may affect muscle strength or function within 12 weeks prior to screening
If laboratory test values are abnormal at the time of screening
Hemoglobin <10 g/dL
Serum albumin <2.5 g/dL
Platelet count <50,000/ml
Abnormal GGT or total bilirubin (>laboratory's upper limit of normal)
Abnormal renal function (Serum creatinine >1.5 Times laboratory's upper limit of normal)"
Those with significant neuromuscular or genetic diseases other than DMD
Those with significant heart, lung, liver, kidney, hematological, immunological, behavioral disease, or other clinically significant diseases including malignant tumors
Those who have a previous or current medical condition that may adversely affect the safety of the subject, make it difficult to complete treatment, or affect the evaluation of clinical trial results at the discretion of the investigator
Those who do not have the will or ability to comply with clinical trial procedures at the discretion of the investigator
Facility Information:
Facility Name
Samsung Medical Center
City
Seoul
Country
Korea, Republic of
12. IPD Sharing Statement
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Determine the Safety and Dose of EN001 in Patients With Duchenne Muscular Dystrophy(DMD)
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