Clinical trial NCT05333406: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Charcot-Marie-Tooth Disease, Type IA
Lead sponsor: ENCell
Sponsor class: INDUSTRY
First posted: 2022-04-19
Enrollment: 9
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product
timeFrame: Week 16 after treatment
measure: Determination of Dose-limiting toxicity (DLT) levels of EN001
timeFrame: Up to Week 4 after dosing on Day 0
measure: Determination of Maximum tolerated dose (MTD) levels of EN001
timeFrame: Up to Week 4 after dosing on Day 0
measure: Number of participants with Vital Signs abnormalities
timeFrame: From screening up to Week 16
measure: Number of participants with clinically significant abnormalities of Physical Examinations
timeFrame: From screening up to Week 16
measure: Number of participants with abnormalities of Laboratory Parameters
timeFrame: From screening up to Week 16
measure: Number of participants with 12-lead Electrocardiography (ECG) abnormalities
timeFrame: From screening to baseline on Day 1 (Predose to end of infusion and 90 min after completion of infusion)
Secondary outcomes:
measure: Incidence of adverse events (AEs)
timeFrame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject)
measure: Number of participants with abnormalities of Vital Signs, Physical Findings, and Laboratory Parameters
timeFrame: From screening to the end of treatment/withdrawal visit (up to approximately 5 years per subject)
measure: Change from baseline in disease severity CMTNS-v2 score
timeFrame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
measure: Change from baseline in gait and balance functions
timeFrame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
measure: Change from baseline in the degree of muscle damage (%)
timeFrame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
measure: Change from baseline in nerve regeneration potential
timeFrame: Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: