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 (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

• Korea, Republic of
  • Seoul, Korea, Republic of, 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
• Genders Eligible for Study: All

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	As assessed using the CMTNS v2 (Charcot Marie Tooth Neuropathy Score version The scores range from 0-36. The severity of disease shall be classified according to scores as mild (≤10), moderate (11 to 20), and severe (>20).	Day 0, 90, 180 and Day 270]
Evaluation of patient's neurological disability	As assessed using the FDS (functional disability scale). normal is 0 point, and if determined as bedridden, it is evaluated as 8 points.	Day 0, 90, 180 and Day 270
Evaluation of the activity level of patients with peripheral neuropathy	As assessed using the overall neuropathy limitation scale (ONLS) leg scale. It 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	This test measures the time required for a subject to walk 10m through the 10-Meter Walking Test (10MWT) v2.2.	Day 0, 90, 180 and Day 270
Changes in fatty infiltration level of lower limb muscles	Imaged via MRI.	Day 0 and Day 270
Evaluation of the presence of a disorder in a neurotransmission pathway.	As assessed using the Nerve Conduction Study (NCS) v2.0	Day 0 and Day 270
Evaluation of the presence of hepatocyte growth factor in the body.	As assessed using Anti-HGF Ab test	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): September 9, 2021

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 (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 28, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Neuromuscular Diseases; Stomatognathic Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Tooth Diseases; Nerve Compression Syndromes; Charcot-Marie-Tooth Disease; 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