A Phase 1, Open-Label, Prospective, Dose-finding Clinical Trial for Evaluation of Safety and Tolerability of Intramuscular Injections of CLZ-2002 for the Treatment of Subjects with Charcot-Marie-Tooth type 1(CMT 1)
This study is the First In Human (FIH) clinical trial for evaluating the safety and tolerability of IM injections of CLZ-2002 in patients with Charcot-Marie-Tooth disease (CMT) Type 1. CLZ-2002 is the allogeneic mesenchymal stem cell-derived Neuronal Regeneration Promoting Cells. These cells are Schwann cell-like cells differentiated from tonsillar mesenchymal stem cells. CLZ-2002 helps the remyelination of the damaged peripheral nerves by restoring the myelin sheaths. It also induces the nerve regeneration and myelination pathways in the sciatic nerve and restores abnormal muscle tissues in Charcot-Marie-Tooth disease type 1 (CMT1).
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
9
Low dose group (6×10\^6 cells), Mid dose group (12×10\^6 cells), High dose group (24×10\^6 cells)
Samsung Medical center
Seoul, Gangnam-gu, South Korea
Safety and tolerability of intramuscular (IM) injections of CLZ-2002 in Participants
Frequency and percentage of treatment-emergent adverse events (TEAEs) and serious adverse events after injection through laboratory tests, physical examinations, vital signs, and electrocardiogram measurements conducted during the clinical trial.
Time frame: Day 1 (visit 2) to Week 24 (visit 6)
Changes from baseline in the disease severity of CMTNS-v2 score at Weeks 4, 12, and 24.
The range of CMTNS-v2 (Charcot Marie Tooth Neuropathy Score-v2) ranges from 0-36. The disease severity is classified as mild (≤10), moderate (11 to 20), and severe (\>21).
Time frame: Weeks 4, 12 and 24
Changes from baseline in neurological examination at Weeks 1, 4, 12 and 24
The principal investigator will assess the neurological examination which is investigated the evidence of muscle weakness in the arms, legs, hands, and feet; as well as signs of muscle wasting, reduced reflexes, and any sensory loss.
Time frame: Weeks 1, 4, 12 and 24
Changes from baseline in the overall neuropathy limitation scale (ONLS) at Weeks 4, 12 and 24
The Overall Neuropathy Limiting Scale (ONLS) assesses scale scores in the lower extremities as the Total Neuropathy Limiting Scale. A 1-point stage represents a clinically meaningful change in terms of disability.
Time frame: Weeks 4, 12 and 24
Changes from baseline in functional disability using the functional disability scale (FDS) at Weeks 4, 12, and 24
The Functional Disability Scale (FDS) primarily evaluates impairment in motor function and is assessed by the neurologist (principal investigator) during the visit. The 9 stages of FDS are as follows: 0; normal, 1; normal but with cramps and fatigability, 2; inability to run, 3; walking difficulty but still possible unaided, 4; If able to walk with a cane (walk with cane), 5; walk with crutches, 6; walk with a walker, 7; wheelchair bound, 8; bedridden.
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Time frame: Weeks 4, 12, and 24
Changes from baseline in the 10-meter walk test at Weeks 4, 12, and 24
This test measures the time required for a subject to walk 10 m through the 10-Meter Walking Test (10MWT)
Time frame: Weeks 4, 12, and 24
Change from baseline in the fatty infiltration level of lower limb muscles at Week 24.
The degree of fat infilteration seen on MRI was classified into five grades from 0-4 and compared as follow: No fat infiltration at all (Grade 0; no fat), some traces of fat infiltration (Grade1; some fatty streak), more muscle than fat (Grade2; fat \<muscle), when muscle and fat are similar (Grade3; fat = muscle), and when fat is more than muscle (Grade 4; fat\>muscle).
Time frame: Week 24
Changes from baseline in the velocity of Motor and Sensory nerve conduction at Weeks 4, 12, and 24
Motor and sensory nerve conduction studies will be performed on the median nerve, ulnar nerve, peroneal nerve, tibial nerve, and sural nerve using skin surface stimulation electrodes and recording electrodes. using the skin surface stimulation and recording method. The studies will be performed with the amplitudes of the compound muscle action potential (CMAP) and the sensory nerve action potential (SNAP) from the positive maximum value to the negative maximum value.
Time frame: Weeks 4, 12, and 24