CMTPhase 1/2NCT05361031
The Safety and Tolerability of Engensis (VM202) in Patients With Charcot-Marie-Tooth Disease Subtype 1A (CMT1A)
A Phase 1/2 study testing Engensis (VM202) in people with CMT, run by Helixmith Co., Ltd. at 1 site in South Korea.
Trial summary
To assess the safety and tolerability of the investigational product Engensis (VM202) injected in the weakened lower limb muscles of CMT1A patients Read more about this study
- Who is it for?
- Ages 19 to 65 years
- Conditions the study is for
- CMT
- What is being tested?
- Engensis (VM202)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSouth Korea
- Study dates
- 21 Sep 2020to 22 Feb 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 19 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females ≥ 19 years of age and ≤ 65 years of age
- Patients with confirmed diagnosis of CMT1A by genetic testing
- Patients with mild to moderate severity assessed by Charcot Marie Tooth Neuropathy Score version 2 (CMTNS v2) with a score > 2 and ≤ 20
- Individuals with lower limb muscle weakness with minimum dorsiflexion or more
- 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
- Individuals who can comply with the requirements in the clinical study
- In case of females of child bearing potential, those who test negative in a urine or serum pregnancy test at screening
- Individuals who practice medically approved contraceptive methods throughout the clinical study
Who cannot join
- 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
- Patients with other neuromuscular diseases or neuropathy-inducing factors: Patients with chronic alcohol addiction, undergoing anticancer chemotherapy, or taking neurotoxic drugs
- Patients diagnosed with diabetes
- Patients diagnosed with inflammatory bowel disease
- Patients with a history of stroke or cerebral ischemic attack within 12 months prior to the screening date
- Patients with a history of coronary artery disease, such as myocardial infarction and unstable angina pectoris, within 12 months prior to the screening date
Show all 25Show fewer
- Morbidly obese patients with body mass index (BMI) ≥ 37
- 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
- Patients who may be affected by the muscle strength measurement test due to ankle contracture or surgery
- Patients with uncontrolled hypertension (if systolic blood pressure is ≥ 160 mmHg or diastolic blood pressure is ≥ 100 mmHg at screening)
- 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)
- 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.
- Patients diagnosed with active pulmonary tuberculosis
- Patients with HBV or HCV
- Patients who test positive in human immunodeficiency virus (HIV) antibody test
- Patients in an immunosuppressive state due to treatments such as immunosuppressants, chemotherapy, and radiotherapy
- Patients with a history of mental disease within 6 months prior to the screening date, which may interfere with participation in the study
- 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
- Individuals who participated in another clinical study within 6 months before the time of screening
- Individuals who have shown significant adverse events such as hypersensitivity reactions to the investigational product
- Pregnant or breastfeeding females
- Other individuals determined ineligible by the principal investigator to participate in the clinical study due to other reasons including clinical laboratory test results
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Samsung Medical Center, Seoul National University Hospital
Seoul, 06351
About this study
Official title: 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
Read the 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.
- Conditions
- CMT
- Being tested
- Engensis (VM202)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Engensis (VM202)Biological
Intramuscular injections
| Study group | Role | What they receive |
|---|---|---|
| Engensis (VM202) | Experimental | 56 (ea) 0.25mg (0.5 mL) injections in each of the left and right lower limbs on Days 0, 14, 90, and 104. Receives: Biological: Engensis (VM202) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 0 visit to the Day 270 visit
Secondary outcomes (7)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: Day 0 and Day 270
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 May 2022
- Study start21 Sep 2020
- Primary completion9 Sep 2021
- Study completion22 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CMTStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single center, repeat dose, open label, phase I/IIA clinical study
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Helixmith Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05361031
- Sponsor's protocol ID
- VMCMT-001
- Status last verified
- Aug 2025
- First submitted
- 31 Mar 2022
- Last updated
- 6 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kwon HM, Kim HS, Chi SA, Nam SH, Kim HJ, Kim SB, Choi BO. An open-label single-arm phase 1/2a study to evaluate the safety and exploratory efficacy of a VM202 in patients with Charcot-Marie-Tooth disease 1A. Orphanet J Rare Dis. 2026 Mar 5;21(1):148. doi: 10.1186/s13023-026-04252-2.
PubMed 41787447
Study at a glance
From the registry record, last updated by the sponsor on 6 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05361031
- Acronym / sponsor ID
- VMCMT-001
- Conditions
- CMT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Helixmith Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 21 Sep 2020 (actual)
- Primary completion
- 9 Sep 2021 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 4 May 2022 (actual)
- Results
- Posted 29 May 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and tolerability of the investigational product Engensis (VM202) injected in the weakened lower limb muscles of CMT1A patients
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single center, repeat dose, open label, phase I/IIA clinical study
| Arm | Type | Receives |
|---|---|---|
| Engensis (VM202) | Experimental | Biological: 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. |
Who may qualify
- Ages
- 19 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females ≥ 19 years of age and ≤ 65 years of age
- Patients with confirmed diagnosis of CMT1A by genetic testing
- Patients with mild to moderate severity assessed by Charcot Marie Tooth Neuropathy Score version 2 (CMTNS v2) with a score > 2 and ≤ 20
- Individuals with lower limb muscle weakness with minimum dorsiflexion or more
- 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
Key exclusion criteria (25 listed)
- 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
- Patients with other neuromuscular diseases or neuropathy-inducing factors: Patients with chronic alcohol addiction, undergoing anticancer chemotherapy, or taking neurotoxic drugs
- Patients diagnosed with diabetes
- Patients diagnosed with inflammatory bowel disease
- Patients with a history of stroke or cerebral ischemic attack within 12 months prior to the screening date
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Engensis (VM202)Intramuscular injections | Biological | Engensis (VM202) |
Primary outcome
Safety of Intramuscular (IM) Injections of Engensis in Participants
Time frame: Day 0 visit to the Day 270 visit
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.
7 secondary outcomes
Evaluation of Severity of Disease Changes Following Engensis Injections - Charcot Marie Tooth Neuropathy Score Version 2
Time frame: Day 0 and Day 270
Evaluation of Patient's Neurological Disability - Functional Disability Score
Time frame: 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
Time frame: Day 0, 90, 180 and Day 270
Evaluation of Patient's Walking Ability - Change From Baseline in the 10-Meter Walk Test
Time frame: Day 0, 90, 180 and Day 270
Changes in Fatty Infiltration Level of Lower Limb Muscles
Time frame: Day 0 and Day 270
Change From Baseline in Nerve Conduction Velocity at Day 270
Time frame: 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.
Time frame: Day 0 and Day 270
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41787447Kwon HM, Kim HS, Chi SA, Nam SH, Kim HJ, Kim SB, Choi BO. An open-label single-arm phase 1/2a study to evaluate the safety and exploratory efficacy of a VM202 in patients with Charcot-Marie-Tooth disease 1A. Orphanet J Rare Dis. 2026 Mar 5;21(1):148. doi: 10.1186/s13023-026-04252-2.
- Individual participant dataSharing planned: No
Related trials for CMT
Not yet recruitingObservational study
Postural Control and Balance Performance in Patients With Carpal Tunnel Syndrome
Carpal Tunnel Syndrome (CTS), Postural Assessment
Active, not recruiting
Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
Neuromuscular Diseases (NMD), Amyotrophic Lateral Sclerosis
RecruitingPhase 2
Study on Thiamine Supplementation to REduce braiN Injury Associated With Chronic Alcohol Use in Outpatients With Alcohol Use Disorder
Alcohol Use Disorder
RecruitingObservational study
Studying Nerve Function and Structure in Charcot-Marie-Tooth Disease, Anti-MAG Neuropathy and CIDP
Charcot-Marie-Tooth, CMT1A
Active, not recruiting
Flexibility, Resistance, Aerobic, Movement Execution Training in Adults With Hereditary Spastic Paraplegia
Hereditary Spastic Paraplegia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Engensis (VM202) in people with CMT, run by Helixmith Co., Ltd. at 1 site in South Korea.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Intramuscular (IM) Injections of Engensis in Participants (time frame: Day 0 visit to the Day 270 visit). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05361031, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.