Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Determine the Safety and Dose of EN001 in Patients With Charcot-Marie-Tooth Disease (CMT) Type 1A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05333406
Recruitment Status : Recruiting
First Posted : April 19, 2022
Last Update Posted : May 13, 2022
Sponsor:
Information provided by (Responsible Party):
ENCell

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

Condition or disease Intervention/treatment Phase
Charcot-Marie-Tooth Disease, Type IA Drug: EN001 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : February 22, 2022
Estimated Primary Completion Date : December 20, 2022
Estimated Study Completion Date : December 31, 2027


Arm Intervention/treatment
Experimental: Dose group A (Low dose)
Participants will receive EN001 intravenously (IV) once on Day 0.
Drug: EN001

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

Other Name: EN001 (allogeneic umbilical cord-derived mesenchymal stem cells)

Experimental: Dose group B (High dose)
Participants will receive EN001 intravenously (IV) once on Day 0.
Drug: EN001

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

Other Name: EN001 (allogeneic umbilical cord-derived mesenchymal stem cells)




Primary Outcome Measures :
  1. Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product [ Time Frame: Week 16 after treatment ]
    Number of participants with treatment-related AEs/SAEs as assessed by CTCAE v5.0

  2. Determination of Dose-limiting toxicity (DLT) levels of EN001 [ Time Frame: Up to Week 4 after dosing on Day 0 ]
    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

  3. Determination of Maximum tolerated dose (MTD) levels of EN001 [ Time Frame: Up to Week 4 after dosing on Day 0 ]
    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.

  4. Number of participants with Vital Signs abnormalities [ Time Frame: From screening up to Week 16 ]

    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).


  5. Number of participants with clinically significant abnormalities of Physical Examinations [ Time Frame: From screening up to Week 16 ]

    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.


  6. Number of participants with abnormalities of Laboratory Parameters [ Time Frame: From screening up to Week 16 ]

    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.


  7. Number of participants with 12-lead Electrocardiography (ECG) abnormalities [ Time Frame: From screening to baseline on Day 1 (Predose to end of infusion and 90 min after completion of infusion) ]
    Measured by result of the ECG measurements and findings


Secondary Outcome Measures :
  1. Incidence of adverse events (AEs) [ Time Frame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject) ]
    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.

  2. Number of participants with abnormalities of Vital Signs, Physical Findings, and Laboratory Parameters [ Time Frame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject) ]
    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.

  3. Change from baseline in disease severity CMTNS-v2 score [ Time Frame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4) ]
    Disease severity measured by CMTNS-v2 score will be collected and analyzed to evaluate the exploratory efficacy of EN001.

  4. Change from baseline in gait and balance functions [ Time Frame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4) ]
    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.

  5. Change from baseline in the degree of muscle damage (%) [ Time Frame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4) ]
    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.

  6. Change from baseline in nerve regeneration potential [ Time Frame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4) ]
    Nerve generation potential measured by MNCV, SNCV, CMAP, and SNAP will be collected and analyzed to evaluate the exploratory efficacy of EN001.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   19 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males and females aged 19 to 75 years old
  2. Those diagnosed with CMT type 1A by a genetic test
  3. Those whose CMTNS-v2 score is more than 2 and 20 or fewer points, and the severity of the disease is mild to moderate
  4. Those who have dorsiflexion muscle weakness
  5. Those who can comply with the requirements for clinical trials
  6. For women of childbearing potential, those who have a negative urine pregnancy test at screening
  7. 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.
  8. 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:

  1. Those with other neuromuscular diseases that the investigator judges cannot participate in the clinical trial
  2. Patients diagnosed with type 1 or type 2 diabetes
  3. Those with a history of stroke or cerebral ischemic attack within 12 months of screening
  4. Those with a history of coronary artery diseases such as myocardial infarction or unstable angina within 12 months of screening
  5. 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
  6. Those who have ankle contractures or have surgery that may affect muscle strength assessment
  7. Those who have experience with stem cell therapy or gene therapy before screening
  8. Those who have participated in clinical trials for chemical synthetic drugs before screening (except when 5 times the half-life has passed)
  9. Patients with uncontrolled hypertension (If the systolic blood pressure is 180 mmHg or higher or the diastolic blood pressure is 110 mmHg or higher)
  10. 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
  11. Those who diagnosed with active pulmonary tuberculosis
  12. Immunosuppressed patients who are taking immunosuppressants, chemotherapy, radiation therapy, etc.
  13. Mental illness patients
  14. Those who are pregnant or lactating
  15. Those with significant heart, lung, liver, kidney, hematological, immunological, behavioral disease, or other clinically significant diseases including malignant tumors
  16. 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
  17. Those who do not have the will or ability to comply with clinical trial procedures at the discretion of the investigator

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05333406


Locations
Layout table for location information
Korea, Republic of
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: ENCell Co., Ltd.    +82-2-6205-8040    encell@encellinc.com   
Sponsors and Collaborators
ENCell
Layout table for additonal information
Responsible Party: ENCell
ClinicalTrials.gov Identifier: NCT05333406    
Other Study ID Numbers: ENCell_2020_02
First Posted: April 19, 2022    Key Record Dates
Last Update Posted: May 13, 2022
Last Verified: May 2022

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn