Clinical trial NCT05338099: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Duchenne Muscular Dystrophy
Lead sponsor: ENCell
Sponsor class: INDUSTRY
First posted: 2022-04-20
Enrollment: 7
Sex: MALE
Minimum age (years): 2
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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).

Eligibility criteria: Inclusion Criteria:

1. Those aged 2 to 18 years old
2. Male
3. Those who are diagnosed with DMD due to a mutation in the dystrophin gene identified by a genetic test
4. Phenotypic evidence of DMD

   * Clinical signs or symptoms (proximal weakness, waddling gait, Gowers maneuver)
   * Elevated serum creatine kinase level
5. 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
6. 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.
7. 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:

1. Those who have clinical signs or symptoms of cardiomyopathy, defined as LVEF \<50% on echocardiography at screening
2. 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)
3. If hepatitis B core antibody and hepatitis C antibody are positive
4. If there is a history of major surgery within 12 weeks or it is expected during the study period
5. Those who have been exposed to gene therapy or genome editing within 24 weeks from the screening
6. Those who have experience with stem cell therapy
7. Those who have been administered Translarna granules (Ataluren) within 24 weeks from the screening
8. Those who are receiving treatment (other than corticosteroids) that may affect muscle strength or function within 12 weeks prior to screening
9. 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)"
10. Those with significant neuromuscular or genetic diseases other than DMD
11. Those with significant heart, lung, liver, kidney, hematological, immunological, behavioral disease, or other clinically significant diseases including malignant tumors
12. 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
13. 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 12 after treatment
measure: Determination of Dose-limiting toxicity (DLT) levels of EN001
timeFrame: Up to Week 2 after dosing on Day 0
measure: Determination of Maximum tolerated dose (MTD) levels of EN001
timeFrame: Up to Week 2 after dosing on Day 0
measure: Number of participants with Vital Signs abnormalities
timeFrame: Week 12 after screening
measure: Number of participants with clinically significant abnormalities of Physical Examinations
timeFrame: From screening up to Week 12
measure: Number of participants with abnormalities of Laboratory Parameters
timeFrame: From screening up to Week 12
measure: Number of participants with abnormalities of 12-lead Electrocardiography (ECG)
timeFrame: From screening to baseline on Day 0 (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: Rate of change at the time of visit compared to baseline (percent [%]) in CK level
timeFrame: From screening up to the end of support (up to approximately 5 years per subject at each visit)
measure: Change from baseline in Function tests
timeFrame: Screening and baseline on Day -1 (up to approximately 5 years per subject after Week 12)
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
Study officials:
References: