Charcot-Marie-Tooth Type 1A
Conditions
Brief summary
This is a randomized, double-blind, placebo-controlled and multicenter 3 phase trial evaluating the therapeutic effect and safety of CMT1A by PXT3003. This double-blind study will assess in parallel groups 1 dose of PXT3003 compared to Placebo in CMT1A patients treated for 15 months.
Detailed description
This multi-center, randomized, double-blind, placebo-controlled, Phase III clinical study is designed to evaluate PXT3003 versus placebo in subjects with genetically confirmed CMT1A of mild-to-moderate severity (CMTNS-V2 score \>2 and ≤18) aged 16 to 65 years. Genetically confirmed CMT1A subjects will be screened and randomized in a 1:1 ratio to receive either oral PXT3003 daily or matching placebo for 15 months. A total of approximately 176 subjects will be enrolled. Visits will take place at Screening (up to -30 days), Baseline , and Months 3, 6, 9, 12, and 15.
Interventions
DRUGPXT3003
Patients will be administered PXT3003 twice daily (bid) at 10mL.
DRUGPXT3003 placebo
Patients will be administered PXT3003 placebo twice daily (bid) at 10mL.
Sponsors
Tasly GeneNet Pharmaceuticals Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Patients aged 16 to 65 years (included boundary value), of either sex; 2. Patients with CMT1A (PMP22 duplication on chromosome 17p11.2) confirmed by gene diagnosis; 3.2 \< CMTNS-v2 score ≤ 18; 4.Patients are dorsalis pedis flexor weakness at least (clinical evaluation); 5.Ulnar nerve motor nerve conductance velocity \> 15 m/s; 6.Subjects participate in clinical trials and sign informed consent voluntarily , and they have the ability to understand as will as abide by research procedures.
Exclusion criteria
1. Being allergic to RS-baclofen, naltrexone HCL, D-sorbitol or any component in pxt3003 excipients or having other serious prior allergic reaction; 2. Existence contraindications of baclofen, naltrexone or sorbitol, such as porphyria; 3. Any other associated cause of peripheral neuropathy such as diabetes mellitus (including diabetes history and glycosylated hemoglobin \>6.5%) 4. Subjects with other neurological diseases affecting the evaluation of study treatment; 5. Patients with the score of ONLS score is 0; 6. A history of unstable medical diseases with clinically significant unstable medical diseases (unstable angina pectoris, tumor, blood disease, hepatitis or liver failure, renal failure, etc.) that may cause harm to the subjects participating in this study in the past 1 year; 7. Limb surgery had implemented within the first six months of randomization or will be planned before the completion of the clinical trial; 8. Hepatic or renal dysfunction: 1. TBIL\>1.5×ULN,ALT\>3×ULN,AST\>3×ULN; 2. Cr\>1.5×ULN; 9. Syphilis antibody and HIV antibody positive subjects; 10. Subjects with tumors indicated by chest radiograph or B-ultrasound; 11. Subjects with alcohol dependence in recent 3 months; 12. Females that are of childbearing potential, pregnant, or are breast-feeding;Subjects who are unable to use appropriate contraceptives during the trial; 13. Subjects with concomitant treatment 4 weeks before enrollment, including but not limited to baclofen, naltrexone, sorbitol, opioids, vitamin C, levothyroxine and potentially neurotoxic drugs (such as amiodarone and chloroquine); 14. Subjects unable to complete the follow-up of study; 15. Participated in another clinical trial and used the test drug within the last 30 days; 16. Different subjects from the same family and living in the same residence can only include one subject, so as to avoid treatment confusion, affect blind treatment and affect the interpretation of the research results; 17. Investigators affirm the compliance in a certain subject is poor or there are some other factors that are not suitable to participate in this clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Neuropathy Limitation Scale (ONLS) score | 15 months | The primary efficacy endpoint will be the main effect of the studied treatment on the improvement of disability measured by the Overall Neuropathy Limitation Scale (ONLS) score, summarized at 15 months defined by: the change of the ONLS from baseline to the 15 months.ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score to measure limitations in the everyday activities of the upper limbs (rated in 5 points) and the lower limbs (rated on 7 points) . The total score goes from 0 ( no disability) to 12 (maximum disability). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS) | 15 months | ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score to measure limitations in the everyday activities of the upper limbs (rated in 5 points) and the lower limbs (rated on 7 points) . The total score goes from 0 ( no disability) to 12 (maximum disability). |
| Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2); | 15 months | CMTNS is a specific scale designed to assess severity of impairment in CMT disease .Although not completely validated, it provides a single and reliable measure of CMT severity. It is a 36-point scale based on 9 items: 5 of them quantify impairment (sensory symptoms, pin sensibility, vibration, arm and leg strength). |
| 10-Meter Walk Test (10MWT); | 15 months | Record the time for walk 10 meters . 10m WT is simple to administer, standardized, reliable and valid evaluation of functional exercise capacity and gait that has been proven reliable in neurologic disorders and in CMT patients. Results recorded are the time to walk 10 meters and the number of steps performed. |
| Treatment responders rate of PXT3003; | 15 months | Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment. |
| Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ; | 15 months | QMT is used to evaluate motor strength in CMT1A. The following muscles will be evaluated: hand grip (right and left). |
| Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side: | 15 months | The assessment parameters including: Distal motor latency (DML) . |
| Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side | 15 months | The assessment parameters including: Nerve conduction velocity (NCV) . |
| Nine-hole peg test (9HPT) for non-dominant hand ; | 15 months | The 9-HPT is a simple timed test of fine motor coordination of extremities in the upper limbs. |
Countries
China
Outcome results
None listed