Back to resultsThe Safety and Tolerability of CLZ-2002 in Patients With Charcot-Marie Tooth Disease.
Primary Purpose
Charcot Marie Tooth Disease, Type 1
Status
Recruiting
Phase
Phase 1
Locations
Korea, Republic of
Study Type
Interventional
Intervention
CLZ-2002
Sponsored by
About this trial
This is an interventional treatment trial for Charcot Marie Tooth Disease, Type 1 focused on measuring Charcot-Marie-Tooth Disease, CMT1, Cell therapy, Tonsillar mesenchymal stem cells (T-MSC), Neuronal Regeneration Promoting Cells, Schwann cell-like cells
Eligibility Criteria
Inclusion Criteria: Subjects aged 18 years or older Subjects with a proven diagnosis of Charcot-Marie-Tooth disease type 1 at the time of screening visit Subjects who have muscle weakness in at least foot dorsiflexion (clinical assessment) at the time of screening visit Subjects with a CMT neuropathy score (CMTNS-v2) of 2 or more and 30 or fewer points at the time of screening visit Subjects who can understand and are willing to sign a written informed consent document are willing to comply with all study procedures and schedule visits. Exclusion Criteria: Subjects who have any other neuromuscular diseases Subjects who have undergone upper and lower limb bone surgery within six months before screening visit Subjects who have concerns about muscle strength measurements due to the previous surgery Subjects who have severe active infection including severe/purulent cellulitis at the injection sites at screening visit Subjects who have a history of hospitalization due to hypersensitivity to antihistamines or allergy or hypersensitivity to certain substances such as food or drugs Subjects who have a history of unstable cardiovascular disease defined by the presence of myocardial infarction (STEMI or NSTEMI) within 6 months before the screening or the presence of unstable angina pectoris (in the case of increased frequency of symptoms, increased severity, or signs of prolonged symptoms at moderate activity or rest) Subjects who have a history of a transient ischemic attack (TIA) or stroke within 6 months before screening visit Subjects who have a positive HIV antibody test, hepatitis B antigen, or hepatitis C antibody test result Subjects who have a history of malignant tumors within 5 years before screening visit Subjects who have received systemic steroids (inhaled steroids are allowed), immunotherapy, or cytotoxic therapy within 14 days before screening, or who are expected to receive such treatment during the study period Subjects who have participated in other clinical trials within 30 days before screening visit Pregnant and lactating women or women of childbearing potential and men who plan a pregnancy or are unwilling to use adequate birth control methods& until 30 days after the end of drug administration
Sites / Locations
- Samsung Medical centerRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
CLZ-2002
Arm Description
CLZ-2002 injection is intramuscular in lower limbs on Day 1.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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).
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.
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.
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.
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)
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).
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.
Full Information
NCT ID
NCT05947578
First Posted
June 16, 2023
Last Updated
July 18, 2023
Sponsor
Cellatoz Therapeutics, Inc
1. Study Identification
Unique Protocol Identification Number
NCT05947578
Brief Title
The Safety and Tolerability of CLZ-2002 in Patients With Charcot-Marie Tooth Disease.
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 19, 2023 (Actual)
Primary Completion Date
May 30, 2024 (Anticipated)
Study Completion Date
November 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Cellatoz Therapeutics, Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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)
Detailed Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Charcot Marie Tooth Disease, Type 1
Keywords
Charcot-Marie-Tooth Disease, CMT1, Cell therapy, Tonsillar mesenchymal stem cells (T-MSC), Neuronal Regeneration Promoting Cells, Schwann cell-like cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Dose group A (Low dose) Dose group B (Mid dose) Dose group C (High dose)
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
CLZ-2002
Arm Type
Experimental
Arm Description
CLZ-2002 injection is intramuscular in lower limbs on Day 1.
Intervention Type
Drug
Intervention Name(s)
CLZ-2002
Other Intervention Name(s)
Allogeneic tonsillar mesenchymal stem cell-derived schwann cell like cells
Intervention Description
Low dose group (6×10^6 cells), Mid dose group (12×10^6 cells), High dose group (24×10^6 cells)
Primary Outcome Measure Information:
Title
Safety and tolerability of intramuscular (IM) injections of CLZ-2002 in Participants
Description
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)
Secondary Outcome Measure Information:
Title
Changes from baseline in the disease severity of CMTNS-v2 score at Weeks 4, 12, and 24.
Description
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
Title
Changes from baseline in neurological examination at Weeks 1, 4, 12 and 24
Description
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
Title
Changes from baseline in the overall neuropathy limitation scale (ONLS) at Weeks 4, 12 and 24
Description
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
Title
Changes from baseline in functional disability using the functional disability scale (FDS) at Weeks 4, 12, and 24
Description
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.
Time Frame
Weeks 4, 12, and 24
Title
Changes from baseline in the 10-meter walk test at Weeks 4, 12, and 24
Description
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
Title
Change from baseline in the fatty infiltration level of lower limb muscles at Week 24.
Description
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
Title
Changes from baseline in the velocity of Motor and Sensory nerve conduction at Weeks 4, 12, and 24
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Subjects aged 18 years or older
Subjects with a proven diagnosis of Charcot-Marie-Tooth disease type 1 at the time of screening visit
Subjects who have muscle weakness in at least foot dorsiflexion (clinical assessment) at the time of screening visit
Subjects with a CMT neuropathy score (CMTNS-v2) of 2 or more and 30 or fewer points at the time of screening visit
Subjects who can understand and are willing to sign a written informed consent document are willing to comply with all study procedures and schedule visits.
Exclusion Criteria:
Subjects who have any other neuromuscular diseases
Subjects who have undergone upper and lower limb bone surgery within six months before screening visit
Subjects who have concerns about muscle strength measurements due to the previous surgery
Subjects who have severe active infection including severe/purulent cellulitis at the injection sites at screening visit
Subjects who have a history of hospitalization due to hypersensitivity to antihistamines or allergy or hypersensitivity to certain substances such as food or drugs
Subjects who have a history of unstable cardiovascular disease defined by the presence of myocardial infarction (STEMI or NSTEMI) within 6 months before the screening or the presence of unstable angina pectoris (in the case of increased frequency of symptoms, increased severity, or signs of prolonged symptoms at moderate activity or rest)
Subjects who have a history of a transient ischemic attack (TIA) or stroke within 6 months before screening visit
Subjects who have a positive HIV antibody test, hepatitis B antigen, or hepatitis C antibody test result
Subjects who have a history of malignant tumors within 5 years before screening visit
Subjects who have received systemic steroids (inhaled steroids are allowed), immunotherapy, or cytotoxic therapy within 14 days before screening, or who are expected to receive such treatment during the study period
Subjects who have participated in other clinical trials within 30 days before screening visit
Pregnant and lactating women or women of childbearing potential and men who plan a pregnancy or are unwilling to use adequate birth control methods& until 30 days after the end of drug administration
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Hyesun Kim
Phone
+82316039726
Email
hskim@cellatozrx.com
Facility Information:
Facility Name
Samsung Medical center
City
Seoul
State/Province
Gangnam-gu
ZIP/Postal Code
06351
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Byung Ok Choi
Phone
+82-2-3410-1296
Email
bochoi77@hanmail.net
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
The Safety and Tolerability of CLZ-2002 in Patients With Charcot-Marie Tooth Disease.
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