Back to resultsDetermine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A
Primary Purpose
Charcot-Marie-Tooth Disease, Type IA
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 Charcot-Marie-Tooth Disease, Type IA
Eligibility Criteria
Inclusion Criteria:
- Males and females aged 19 to 75 years old
- Those diagnosed with CMT type 1A by a genetic test
- Those whose CMTNS-v2 score is more than 2 and 20 or fewer points, and the severity of the disease is mild to moderate
- Those who have dorsiflexion muscle weakness
- Those who can comply with the requirements for clinical trials
- For women of childbearing potential, those who have a negative urine pregnancy test at screening
- Those who use a medically acceptable method of contraception until clinical trial visit 7 (short-term follow-up visit, 16 weeks): hormonal contraception, intrauterine device (IUD), intrauterine system (IUS), vasectomy, tubal ligation, or double barrier method using a cervical cap or a diaphragm with a male condom.
- Those who voluntarily agree to participate in this study and sign an IRB-approved consent form after being informed about the characteristics of this clinical trial prior to all screening tests
Exclusion Criteria:
- Those with other neuromuscular diseases that the investigator judges cannot participate in the clinical trial
- Patients diagnosed with type 1 or type 2 diabetes
- Those with a history of stroke or cerebral ischemic attack within 12 months of screening
- Those with a history of coronary artery diseases such as myocardial infarction or unstable angina within 12 months of screening
- Those who have undergone orthopedic surgery on the lower extremities (bone and ligament correction, artificial joint insertion, osteotomy, arthroscopic surgery) within 6 months of screening
- Those who have ankle contractures or have surgery that may affect muscle strength assessment
- Those who have experience with stem cell therapy or gene therapy before screening
- Those who have participated in clinical trials for chemical synthetic drugs before screening (except when 5 times the half-life has passed)
- Patients with uncontrolled hypertension (If the systolic blood pressure is 180 mmHg or higher or the diastolic blood pressure is 110 mmHg or higher)
- If there is a history of malignant tumors other than basal cell carcinoma or squamous cell carcinoma occurring in the skin within 5 years of screening
- Those who diagnosed with active pulmonary tuberculosis
- Immunosuppressed patients who are taking immunosuppressants, chemotherapy, radiation therapy, etc.
- Mental illness patients
- Those who are pregnant or lactating
- 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 0.
Participants will receive EN001 intravenously (IV) once on Day 0.
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 AEs/SAEs as assessed by CTCAE v5.0
Determination of Dose-limiting toxicity (DLT) levels of EN001
Among the adverse events occurring for 4 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE v5.0
Determination of Maximum tolerated dose (MTD) levels of EN001
Among the adverse events occurring for 4 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE v5.0 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 12-lead Electrocardiography (ECG) abnormalities
Measured by result of the ECG measurements and findings
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.
Change from baseline in disease severity CMTNS-v2 score
Disease severity measured by CMTNS-v2 score will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Change from baseline in gait and balance functions
Gait and balance functions measured by Ten Meter Walking Test(10MWT), Functional Disability Scale (FDS), and Overall Neuropathy Limitation Score (ONLS) leg scale will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Change from baseline in the degree of muscle damage (%)
The degree of muscle damage measured by lower extremity magnetic resonance imaging (MRI) scan will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Change from baseline in nerve regeneration potential
Nerve generation potential measured by MNCV, SNCV, CMAP, and SNAP will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05333406
Brief Title
Determine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A
Official Title
Open-label, Dose-escalation, Phase 1 Clinical Trial to Determine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Completed
Study Start Date
February 22, 2022 (Actual)
Primary Completion Date
December 20, 2022 (Actual)
Study Completion Date
December 20, 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 Charcot-Marie-Tooth disease (CMT) type 1A
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 Charcot-Marie-Tooth disease (CMT) type 1A.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Charcot-Marie-Tooth Disease, Type IA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
9 (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 0.
Arm Title
Dose group B (High dose)
Arm Type
Experimental
Arm Description
Participants will receive EN001 intravenously (IV) once on Day 0.
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 Charcot-Marie-Tooth disease (CMT) type 1A 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 Charcot-Marie-Tooth disease (CMT) type 1A 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 AEs/SAEs as assessed by CTCAE v5.0
Time Frame
Week 16 after treatment
Title
Determination of Dose-limiting toxicity (DLT) levels of EN001
Description
Among the adverse events occurring for 4 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE v5.0
Time Frame
Up to Week 4 after dosing on Day 0
Title
Determination of Maximum tolerated dose (MTD) levels of EN001
Description
Among the adverse events occurring for 4 weeks after administration of the investigational product, Grade 3 or higher adverse events according to CTCAE v5.0 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 4 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
From screening up to Week 16
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 16
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 16
Title
Number of participants with 12-lead Electrocardiography (ECG) abnormalities
Description
Measured by result of the ECG measurements and findings
Time Frame
From screening to baseline on Day 1 (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
Change from baseline in disease severity CMTNS-v2 score
Description
Disease severity measured by CMTNS-v2 score will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Time Frame
Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
Title
Change from baseline in gait and balance functions
Description
Gait and balance functions measured by Ten Meter Walking Test(10MWT), Functional Disability Scale (FDS), and Overall Neuropathy Limitation Score (ONLS) leg scale will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Time Frame
Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
Title
Change from baseline in the degree of muscle damage (%)
Description
The degree of muscle damage measured by lower extremity magnetic resonance imaging (MRI) scan will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Time Frame
Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
Title
Change from baseline in nerve regeneration potential
Description
Nerve generation potential measured by MNCV, SNCV, CMAP, and SNAP will be collected and analyzed to evaluate the exploratory efficacy of EN001.
Time Frame
Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
19 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Males and females aged 19 to 75 years old
Those diagnosed with CMT type 1A by a genetic test
Those whose CMTNS-v2 score is more than 2 and 20 or fewer points, and the severity of the disease is mild to moderate
Those who have dorsiflexion muscle weakness
Those who can comply with the requirements for clinical trials
For women of childbearing potential, those who have a negative urine pregnancy test at screening
Those who use a medically acceptable method of contraception until clinical trial visit 7 (short-term follow-up visit, 16 weeks): hormonal contraception, intrauterine device (IUD), intrauterine system (IUS), vasectomy, tubal ligation, or double barrier method using a cervical cap or a diaphragm with a male condom.
Those who voluntarily agree to participate in this study and sign an IRB-approved consent form after being informed about the characteristics of this clinical trial prior to all screening tests
Exclusion Criteria:
Those with other neuromuscular diseases that the investigator judges cannot participate in the clinical trial
Patients diagnosed with type 1 or type 2 diabetes
Those with a history of stroke or cerebral ischemic attack within 12 months of screening
Those with a history of coronary artery diseases such as myocardial infarction or unstable angina within 12 months of screening
Those who have undergone orthopedic surgery on the lower extremities (bone and ligament correction, artificial joint insertion, osteotomy, arthroscopic surgery) within 6 months of screening
Those who have ankle contractures or have surgery that may affect muscle strength assessment
Those who have experience with stem cell therapy or gene therapy before screening
Those who have participated in clinical trials for chemical synthetic drugs before screening (except when 5 times the half-life has passed)
Patients with uncontrolled hypertension (If the systolic blood pressure is 180 mmHg or higher or the diastolic blood pressure is 110 mmHg or higher)
If there is a history of malignant tumors other than basal cell carcinoma or squamous cell carcinoma occurring in the skin within 5 years of screening
Those who diagnosed with active pulmonary tuberculosis
Immunosuppressed patients who are taking immunosuppressants, chemotherapy, radiation therapy, etc.
Mental illness patients
Those who are pregnant or lactating
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 Charcot-Marie-Tooth Disease (CMT) Type 1A
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