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

NCT05333406 | Completed Phase 1

• 1 other identifier: ENCell_2020_02
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

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

Conditions

Charcot-Marie-Tooth Disease, Type IA

Outcome Measures

Primary Outcomes (7)

• 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

  Week 16 after treatment

• 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

  Up to Week 4 after dosing on Day 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.

  Up to Week 4 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).

  From screening up to Week 16

• 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.

  From screening up to Week 16

• 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.

  From screening up to Week 16

• Number of participants with 12-lead Electrocardiography (ECG) abnormalities

  Measured by result of the ECG measurements and findings

  From screening to baseline on Day 1 (Predose to end of infusion and 90 min after completion of infusion)

Secondary Outcomes (6)

• Incidence of adverse events (AEs)

  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

  From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject)

• Change from baseline in disease severity CMTNS-v2 score

  Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)

• Change from baseline in gait and balance functions

  Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)

• Change from baseline in the degree of muscle damage (%)

  Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)

Study Arms (2)

Dose group A (Low dose)

EXPERIMENTAL

Participants will receive EN001 intravenously (IV) once on Day 0.

Drug: EN001

Dose group B (High dose)

EXPERIMENTAL

Participants will receive EN001 intravenously (IV) once on Day 0.

Drug: EN001

Interventions

EN001 DRUG

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

Also known as: EN001 (allogeneic umbilical cord-derived mesenchymal stem cells)

Dose group A (Low dose)

Eligibility Criteria

• Age: 19 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ENCell: lead

Study Sites (1)

Samsung Medical Center

Seoul, South Korea

Location

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2022
• First Posted: April 19, 2022
• Study Start: February 22, 2022
• Primary Completion: December 20, 2022
• Study Completion: December 20, 2022
• Last Updated: February 17, 2023

Record last verified: 2023-02

Locations

KR (1)