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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Dose group A (Low dose)
Participants will receive EN001 intravenously (IV) once on Day 0.
干预措施: EN001 (Drug)
Dose group B (High dose)
Participants will receive EN001 intravenously (IV) once on Day 0.
干预措施: EN001 (Drug)
结局指标
主要结局
Number of participants of any Adverse Events (AEs)/Serious Adverse Events (SAEs) related investigational product
时间窗: Week 16 after treatment
Number of participants with treatment-related AEs/SAEs as assessed by CTCAE v5.0
Determination of Dose-limiting toxicity (DLT) levels of EN001
时间窗: 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
Determination of Maximum tolerated dose (MTD) levels of EN001
时间窗: 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.
Number of participants with Vital Signs abnormalities
时间窗: 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).
Number of participants with clinically significant abnormalities of Physical Examinations
时间窗: 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.
Number of participants with abnormalities of Laboratory Parameters
时间窗: 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.
Number of participants with 12-lead Electrocardiography (ECG) abnormalities
时间窗: 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
次要结局
- 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))
- 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 nerve regeneration potential(Screening and baseline on Day 0 (up to approximately 5 years per subject after Week 4))