A Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A

A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Phase III Study to Assess the Efficacy and Safety of PXT3003 in Charcot-Marie-Tooth Type 1A (CMT1A) Treated 15 Months

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.

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.

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.