Evaluate the Safety and Efficacy of EN001 in Patients With Charcot-Marie-Tooth Disease Type 1A

Last updated: March 18, 2024
Sponsor: ENCell
Overall Status: Active - Recruiting

Phase

1

Condition

Neuropathy

Peripheral Neuropathy

Treatment

EN001

Clinical Study ID

NCT06328712
EN001_MIRACLE1
  • Ages > 19
  • All Genders

Study Summary

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)

Eligibility Criteria

Inclusion

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:
  4. Genetic diagnosis: CMT1A type
  5. 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.
  1. Women and men of childbearing potential who have agreed to use the appropriatecontraceptive method(s) outlined in the protocol during the clinical trial period.
  • Appropriate contraception is defined as follows and is achieved by applying oneor 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 contraceptivemethods [hormonal contraceptives (oral contraceptives, subcutaneouscontraceptives (Implanon, etc.), long-acting contraceptive injections,emergency contraceptive pills), implantation of an intrauterine device orintrauterine system (Loop, Mirena), Infertility procedures (vasectomy, tuballigation, etc.)]
  • Abstinence: Absolute abstinence. If, in the examiner's judgment, thesubject's age, occupation, lifestyle, or sexual orientation warrantscontraception, strict abstinence from sexual intercourse is also acceptable.However, periodic abstinence (e.g. Karenda method, ovulation method,symptomatic temperature method), abstinence, and external vaginalejaculation are not recognized as appropriate contraceptive methods.

Exclusion

Exclusion Criteria:

  1. Those with the following comorbidities confirmed at the time of screening
  2. Subjects with neuromuscular diseases other than CMT1A or neuropathy- inducingfactors (uremia) that may affect the safety and efficacy evaluation of thisclinical trial, according to the judgment of the investigator.
  3. Individuals diagnosed with type 1 or type 2 diabetes
  4. Individuals diagnosed with active pulmonary tuberculosis
  5. Patients with uncontrolled hypertension (systolic blood pressure over 180 mmHg ordiastolic blood pressure over 110 mmHg)
  6. Subjects with other clinically significant diseases, including significant heart,lung, liver, kidney, hematological, immunological or behavioral diseases ormalignant tumors, according to the investigator's judgment
  7. Individuals who display the specified test abnormalities in laboratory tests atthe 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) ispositive (If anti-HBc positive) However, registration is possible if the HBVDNA test result is negative. (If anti-HCV positive) However, registration ispossible if the HCV RNA test result is negative.
  1. Those who have ankle contracture or have undergone surgery that may affect musclestrength measurement tests
  2. Medical history and surgical history
  3. Those who have undergone orthopedic surgery (bone or ligament correction,artificial joint implantation, osteotomy, arthroscopic surgery) on the lowerextremities within 24 weeks before screening
  4. Those with a history of stroke or cerebral ischemic attack within 48 weeks beforescreening
  5. Those with a history of coronary artery disease, such as myocardial infarction orincomplete angina, within 48 weeks before screening
  6. Those with a history of malignant tumor within 240 weeks before screening (excluding basal cell carcinoma or squamous cell carcinoma that occurs on theskin)
  7. Drugs and therapies prohibited from concurrent use
  8. Those who participated in another clinical trial and administered/appliedclinical trial drugs/medical devices within 4 weeks before screening
  9. Those who administered/applied immunosuppressants, chemotherapy, radiationtherapy, etc. within 12 weeks before screening
  10. Persons who have administered cell therapy or gene therapy throughout their lives
  11. Persons who have administered neurotoxic drugs that can accelerate peripheralnerve 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
  1. Persons with hypersensitivity to the components of clinical investigational products
  2. Those who have had metal substances (heart pacemaker, nerve stimulator, cochlearimplant, etc.) implanted in their body
  3. Pregnant, lactating, or planning to become pregnant during the clinical trial period
  4. Subjects with a psychiatric disorder (anxiety disorder, claustrophobia, or othersignificant mental disorder) or a history of drug and alcohol abuse that may affectthe clinical trial, according to the judgment of the investigator.
  5. Those who are deemed inappropriate to participate in clinical trials according to thejudgment of the investigator

Study Design

Total Participants: 12
Treatment Group(s): 1
Primary Treatment: EN001
Phase: 1
Study Start date:
March 01, 2024
Estimated Completion Date:
October 31, 2024

Study Description

This clinical trial is a phase 1b clinical trial with a 3+3 dose escalation design to evaluate the safety, including tolerability, of EN001 and explore efficacy.

The study was designed using the traditional 3+3 dose escalation method to confirm the maximum tolerated dose (MTD) and determine the recommended phase 2 dose (RP2D).

Dose increase is carried out until the maximum tolerated dose (MTD) is confirmed at a dose of 2.5 × 10^6 cells/kg (Cohort 2) or less, which is the maximum planned dose (MPD). The maximum tolerated dose (MTD) is defined as the highest dose at which the incidence of dose limiting toxicity (DLT) is lower than 33%. To determine the maximum tolerated dose (MTD), 3-6 test subjects from each dose cohort are enrolled and EN001 is administered twice at 4-week intervals, and dose-limiting toxicity (DLT) is evaluated until 4 weeks (visit 6).

The safety review committee (SRC) is comprised of the principal investigator, sponsor, etc. as members, and EN001 confirmed by the end of each cohort (end of dose-limiting toxicity (DLT) evaluation of the last dosed subject in the cohort). Safety data are comprehensively reviewed to determine all matters related to dose, such as increase or decrease in dose, and finally the recommended phase 2 dose (RP2D) is determined.

In addition, test subjects participating in phase 1b will be followed up for safety and effectiveness for 5 years from the time of EN001 administration according to the long-term follow-up protocol.

Connect with a study center

  • Samsung Medical Center

    Seoul,
    Korea, Republic of

    Active - Recruiting

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