To assess the safety and tolerability of the investigational product Engensis (VM202) injected in the weakened lower limb muscles of CMT1A patients
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
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Intramuscular injections
Samsung Medical Center, Seoul National University Hospital
Seoul, South Korea
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.
Time frame: Day 0 visit to the Day 270 visit
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.
Time frame: 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.
Time frame: Day 0, 90, 180 and Day 270
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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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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.
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
Time frame: Day 0 and Day 270