Evaluating EN001 for Charcot-Marie-Tooth Disease Type 1A

An Open, Dose-escalation, Phase 1b Clinical Trial to Evaluate the Safety and Efficacy of EN001 in Patients With Charcot-Marie-Tooth Disease Type 1A (CMT1A)

This study is testing a new treatment called EN001 to see if it is safe and effective for people with Charcot-Marie-Tooth Disease Type 1A.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (estimated)
• Ages: 19 Years and up
• Sex: All
• Sponsor: ENCell (Industry-sponsored)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Seoul)
• Trial ID: NCT06328712 on ClinicalTrials.gov

What this trial studies

This clinical trial is designed to assess the safety and efficacy of EN001 in patients diagnosed with Charcot-Marie-Tooth Disease Type 1A. It employs a 3+3 dose escalation methodology to identify the maximum tolerated dose (MTD) and the recommended phase 2 dose (RP2D). Participants will receive EN001 twice at four-week intervals, and their safety and effectiveness will be monitored for five years following treatment. The study aims to gather comprehensive safety data to inform future phases of research.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 19 years or older with a confirmed genetic diagnosis of CMT1A and specific clinical symptoms.

Not a fit: Patients with other types of Charcot-Marie-Tooth disease or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients suffering from Charcot-Marie-Tooth Disease Type 1A.

How similar studies have performed: While this approach is novel for CMT1A, similar dose escalation studies in other conditions have shown promising results.

Eligibility criteria

Inclusion Criteria:

1. Individuals who have voluntarily agreed to participate in this clinical trial.
2. Men and women aged 19 years or older at the time of providing written consent.
3. Individuals who meet all of the following genetic and clinical diagnostic criteria:

   1. Genetic diagnosis: CMT1A type
   2. Clinical diagnosis:

      * Those with a CMT Neuropathy Score version 2 (CMTNSv2) between 2 or more and 20 or less.
      * Those experiencing muscle weakness due to foot dorsiflexion impairment.
4. Women and men of childbearing potential who have agreed to use the appropriate contraceptive method(s) outlined in the protocol during the clinical trial period.

   * Appropriate contraception is defined as follows and is achieved by applying one or more methods of contraception.

     * Hormonal contraceptives
     * Implantation of an intrauterine device or intrauterine system
     * Sterilization procedures (vasectomy, tubal ligation, etc.)
     * Double contraceptive method: male condom along with other contraceptive methods \[hormonal contraceptives (oral contraceptives, subcutaneous contraceptives (Implanon, etc.), long-acting contraceptive injections, emergency contraceptive pills), implantation of an intrauterine device or intrauterine system (Loop, Mirena), Infertility procedures (vasectomy, tubal ligation, etc.)\]
     * Abstinence: Absolute abstinence. If, in the examiner's judgment, the subject's age, occupation, lifestyle, or sexual orientation warrants contraception, strict abstinence from sexual intercourse is also acceptable. However, periodic abstinence (e.g. Karenda method, ovulation method, symptomatic temperature method), abstinence, and external vaginal ejaculation are not recognized as appropriate contraceptive methods.

Exclusion Criteria:

1. Those with the following comorbidities confirmed at the time of screening

   1. Subjects with neuromuscular diseases other than CMT1A or neuropathy- inducing factors (uremia) that may affect the safety and efficacy evaluation of this clinical trial, according to the judgment of the investigator.
   2. Individuals diagnosed with type 1 or type 2 diabetes
   3. Individuals diagnosed with active pulmonary tuberculosis
   4. Patients with uncontrolled hypertension (systolic blood pressure over 180 mmHg or diastolic blood pressure over 110 mmHg)
   5. Subjects with other clinically significant diseases, including significant heart, lung, liver, kidney, hematological, immunological or behavioral diseases or malignant tumors, according to the investigator's judgment
   6. Individuals who display the specified test abnormalities in laboratory tests at the time of screening:

      * AST or ALT \> 3 x ULN
      * Total bilirubin\> 1.5 x ULN
      * Serum creatinine \> 1.5 x ULN
      * Any one of the serum virus tests (HBsAg, anti-HBc, anti-HCV, HIV Ag/Ab) is positive (If anti-HBc positive) However, registration is possible if the HBV DNA test result is negative. (If anti-HCV positive) However, registration is possible if the HCV RNA test result is negative.
   7. Those who have ankle contracture or have undergone surgery that may affect muscle strength measurement tests
2. Medical history and surgical history

   1. Those who have undergone orthopedic surgery (bone or ligament correction, artificial joint implantation, osteotomy, arthroscopic surgery) on the lower extremities within 24 weeks before screening
   2. Those with a history of stroke or cerebral ischemic attack within 48 weeks before screening
   3. Those with a history of coronary artery disease, such as myocardial infarction or incomplete angina, within 48 weeks before screening
   4. Those with a history of malignant tumor within 240 weeks before screening (excluding basal cell carcinoma or squamous cell carcinoma that occurs on the skin)
3. Drugs and therapies prohibited from concurrent use

   1. Those who participated in another clinical trial and administered/applied clinical trial drugs/medical devices within 4 weeks before screening
   2. Those who administered/applied immunosuppressants, chemotherapy, radiation therapy, etc. within 12 weeks before screening
   3. Persons who have administered cell therapy or gene therapy throughout their lives
   4. Persons who have administered neurotoxic drugs that can accelerate peripheral nerve damage

      * Platinum series: cisplatin, carboplatin, oxaliplatin
      * Taxane series: paclitaxel, docetaxel
      * Proteasome inhibitors: bortezomib, carfilzomib, ixazomib, etc.
      * thalidomide and derivatives: thalidomide, lenalidomide, pomalidomide
      * Vinca alkaloid series: vincristine, vinblastine, vindesine, vinorelbine
      * Antiarrhythmic drug: amiodarone
      * Anti-inflammatory and antibiotic: colchicine, nitrofurantoin
      * Antiretroviral drugs: zalcitabine, stavudine
      * Others: dichloroacetate, tacrolimus, suramin
4. Persons with hypersensitivity to the components of clinical investigational products
5. Those who have had metal substances (heart pacemaker, nerve stimulator, cochlear implant, etc.) implanted in their body
6. Pregnant, lactating, or planning to become pregnant during the clinical trial period
7. Subjects with a psychiatric disorder (anxiety disorder, claustrophobia, or other significant mental disorder) or a history of drug and alcohol abuse that may affect the clinical trial, according to the judgment of the investigator.
8. Those who are deemed inappropriate to participate in clinical trials according to the judgment of the investigator

Where this trial is running

Seoul

• Samsung Medical Center — Seoul, Korea, Republic of (Recruiting)

Study contacts

• Study coordinator: ENCell

Conditions Charcot-Marie-Tooth Disease Type 1A