The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)

Single Center, Open Label, Repeat Intramuscular Administration, 270 Days, Phase I/2a Clinical Trial to Evaluate Safety, Tolerability of Investigational Product (Engensis: VM202) With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)

To assess the safety and tolerability of the investigational product Engensis (VM202) injected in the weakened lower limb muscles of CMT1A patients

Study Overview

• Status: Completed
• Conditions: CMT
• Intervention / Treatment: Biological: Engensis (VM202)

Detailed Description

There are no therapeutic agents for CMT to date. Attempts were made to develop therapeutic agents, but efficacy could not be demonstrated in clinical studies. Most of the attempted developments for therapeutic agents targeted alleviating the symptoms of CMT1A by regulating the expression of PMP22. This study will use Engensis (VM202), which is a DNA plasmid that contains novel genomic cDNA hybrid human HGF coding sequence (HGF-X7) expressing two isoforms of HGF, HGF 728 and HGF 723. HGF has been thought of as an angiogenic factor, but it has been recently identified as serving the role of a neurotrophic factor. Moreover, it has been reported that it can contribute to muscle tissue regeneration by targeting on muscles. Considering the pathologic mechanism of CMT, the biological activity of HGF helps peripheral nerve regeneration, relieves muscle atrophy, and reduces pain, so it is highly likely to show a therapeutic effect for CMT.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• South Korea
  • Seoul, South Korea, 06351
    • Samsung Medical Center, Seoul National University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males or females ≥ 19 years of age and ≤ 65 years of age
2. Patients with confirmed diagnosis of CMT1A by genetic testing
3. Patients with mild to moderate severity assessed by Charcot Marie Tooth Neuropathy Score version 2 (CMTNS v2) with a score > 2 and ≤ 20
4. Individuals with lower limb muscle weakness with minimum dorsiflexion or more
5. Individuals who voluntarily consented to participate in this study and signed the IRB approved informed consent form after listening to a description on the characteristics of this clinical study prior to all screening tests
6. Individuals who can comply with the requirements in the clinical study
7. In case of females of child bearing potential, those who test negative in a urine or serum pregnancy test at screening
8. Individuals who practice medically approved contraceptive methods throughout the clinical study

Exclusion Criteria:

1. Patients with significant respiratory, circulatory, renal, gastrointestinal, hepatic, endocrine, hematologic, psychiatric disorders or other severe diseases, or alcohol or drug addiction who may develop safety issues or cause confusion in the interpretation of the clinical study results as determined by the principal investigator
2. Patients with other neuromuscular diseases or neuropathy-inducing factors: Patients with chronic alcohol addiction, undergoing anticancer chemotherapy, or taking neurotoxic drugs
3. Patients diagnosed with diabetes
4. Patients diagnosed with inflammatory bowel disease
5. Patients with a history of stroke or cerebral ischemic attack within 12 months prior to the screening date
6. Patients with a history of coronary artery disease, such as myocardial infarction and unstable angina pectoris, within 12 months prior to the screening date
7. Morbidly obese patients with body mass index (BMI) ≥ 37
8. Patients who underwent orthopedic surgery (corrective surgery for bone and ligament, artificial joint implantation, osteosynthesis, osteotomy, arthroscopic surgery) in the lower limbs within 6 months prior to the screening date
9. Patients who may be affected by the muscle strength measurement test due to ankle contracture or surgery
10. Patients with uncontrolled hypertension (if systolic blood pressure is ≥ 160 mmHg or diastolic blood pressure is ≥ 100 mmHg at screening)
11. Patients or patient's immediate family members (parents, siblings, offspring) with a history of malignant tumors within the last 5 years prior to the screening date, excluding basal cell carcinoma or squamous cell carcinoma that occurs on the skin (if it is determined that there is no possibility of relapse after resection), or with a family history of familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC)

12. Patients who have not completed a national cancer screening program applicable to their sex and age (if it cannot be confirmed that the relevant test was received at a national cancer screening center or a recognized screening center)

    However, if it is confirmed that the relevant test was received at a national cancer screening center or a recognized screening center during the screening period, and that the results were within normal range, the patients may participate in the clinical study.

    Common to males and females: If a patient is ≥ 50 years of age, the results of a colonoscopy within 5 years prior to the screening must be determined as being within normal range, and if adenomatous polyps are evident, the results of a colonoscopy within 1 year must be determined as being within normal range (inflammatory polyps or hyperplastic polyps are included in the normal range). If a patient is ≥ 40 years of age, the results of a gastroscopy within 2 years prior to the screening must be within normal range. If a patient is ≥ 54 years of age and has a 30 pack-year history of smoking or more, the results of a low-dose chest CT within 2 years prior to the screening must be within normal range. In case of liver cancer, carriers of hepatitis B or hepatitis C virus and patients with hepatic cirrhosis fall under the exclusion criteria.

    Females: For females ≥ 40 years of age, normal range findings must be confirmed in a mammogram within 2 years. For females ≥ 20 years of age, normal range findings must be confirmed in a Pap smear within 2 years.

13. Patients diagnosed with active pulmonary tuberculosis
14. Patients with HBV or HCV
15. Patients who test positive in human immunodeficiency virus (HIV) antibody test
16. Patients in an immunosuppressive state due to treatments such as immunosuppressants, chemotherapy, and radiotherapy
17. Patients with a history of mental disease within 6 months prior to the screening date, which may interfere with participation in the study
18. Patients who must take medications, that are known to have significant drug interactions within 14 days after the first administration of the investigational product or deemed unsuitable by the investigator's judgment
19. Individuals who participated in another clinical study within 6 months before the time of screening
20. Individuals who have shown significant adverse events such as hypersensitivity reactions to the investigational product
21. Pregnant or breastfeeding females
22. Other individuals determined ineligible by the principal investigator to participate in the clinical study due to other reasons including clinical laboratory test results

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Engensis (VM202); 56 (ea) 0.25mg (0.5 mL) injections in each of the left and right lower limbs on Days 0, 14, 90, and 104.	Biological: Engensis (VM202); Intramuscular injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of Intramuscular (IM) Injections of Engensis in Participants	Frequency and percentage of treatment-emergent adverse events (TEAEs) and serious adverse events after injections, injection site reactions, vital sign, and clinically significant laboratory values for Engensis.	Day 0 visit to the Day 270 visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of Severity of Disease Changes Following Engensis Injections - Charcot Marie Tooth Neuropathy Score Version 2	Charcot-Marie-Tooth Neuropathy Score version 2 is a measurement tool for evaluating the severity of disease. The scoring system is the total neuropathy score, by assessing the symptoms of Charcot-Marie-Tooth patients due to sensory impairment. Measurements were performed in three items for the symptoms of disease, four items for the signs, and two items for neurophysiological testing, a total of nine separate test items. The Total Severity Score is the summed scores of all subscores and has a total minimum score of 0 and a maximum score of 36. The Total Severity Score Scale of the disease is classified according to the Total Score as either mild (0 to 10), moderate (11 to 20), or severe (20 to 36). The Change from Baseline Total Severity Score is the difference between the Day 0 and the Day 270 scores. A negative difference in the Total Severity Score Change from Baseline to Day 270, indicates an improvement of the treated groups' total severity level.	Day 0 and Day 270
Evaluation of Patient's Neurological Disability - Functional Disability Score	Change from Baseline (Day 0) in Functional Disability Scale at Days 90, 180, and 270; as assessed using the Functional Disability Scale 0 - 8 points, where normal is 0 point, best case, and if determined as bedridden, it is evaluated as 8 points, worst case. 0=normal; 1=cramps and fatigability; 2=inability to run; 3=possible unaided; 4=with cane; 5=with crutch; 6=with walker; 7=wheelchair; 8=bedridden. Changes in severity of disease: Functional Disability Scale - Intent-to-Treat population.	Day 0, 90, 180 and Day 270
Evaluation of the Activity Level of Patients With Peripheral Neuropathy Using the Overall Neuropathy Limitation Score Leg Scale	Change from baseline (Day 0) in the overall neuropathy limitation score leg scale at Days 90, 180, and 270. The Overall Neuropathy Limitation Score is scored from 0 to 7. The worst score, 7 points, is defined as restricted to wheelchair, or bed most of the day, unable to make any purposeful movements of the leg.	Day 0, 90, 180 and Day 270
Evaluation of Patient's Walking Ability - Change From Baseline in the 10-Meter Walk Test	This test measures the time in seconds required for a subject to walk 10 meters through the 10-Meter Walking Test version 2.2. Changes in the Mean Time in seconds for lower limb function assessment: 10 Meter Walk Test - Intent to Treat population, from Day 0 to Days 90, 180, and 270. The larger the change in time (Seconds) from Day 0 to Visit date indicates a worsening of the patients walking ability.	Day 0, 90, 180 and Day 270
Changes in Fatty Infiltration Level of Lower Limb Muscles	Changes from baseline (Day 0) in the fat content of lower limb muscles at Day 270. The muscles of lower limbs were imaged with Magnetic Resonance Imaging leg scan, and the degree of fatty infiltration of the leg muscles injected with the investigational product was measured and valuated as fat content value (percent) at one level for each muscle. The six MRI imaging sites to be measured were as follows: peroneus longus left/right, gastrocnemius left/right, and tibialis anterior left/right.	Day 0 and Day 270
Change From Baseline in Nerve Conduction Velocity at Day 270	Change from baseline in Nerve Conduction Velocity to Day 270, for evaluation of the presence of a disorder in a neurotransmission pathway, as assessed using the Nerve Conduction Study version 2.0 Nerve regeneration potential (Electroneurography): Nerve Conduction Velocity (measured in meters per second) - Intent-to-Treat population. Larger negative change from baseline values indicates a slowing of the Nerve Conduction Velocity which is a worsening of the electroconduction function of the specified nerve.	Day 0 and Day 270
Numbers of Participants With and Without Hepatocyte Growth Factor Antibody Generation in the Body at Baseline (Day 0) and Day 270.	The presence of hepatocyte growth factor antibody generation by Engensis (VM202) assessed using anti-hepatocyte growth factor antibody test at Day 0 and Day 270	Day 0 and Day 270

Collaborators and Investigators

• Sponsor: Helixmith Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2020
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): February 22, 2022

Study Registration Dates

• First Submitted: March 31, 2022
• First Submitted That Met QC Criteria: April 28, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Estimated): October 6, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Stomatognathic Diseases; Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
• Other Study ID Numbers: VMCMT-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No