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.

Study Overview

• Status: Completed
• Conditions: Charcot-Marie-Tooth Type 1A
• Intervention / Treatment: Drug: PXT3003; Drug: PXT3003 placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 176
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China
    • Peking University Third Hospital
  • Beijing, China
    • Xuanwu Hospital Capital Medical University
  • Changchun, China
    • The First Bethune Hospital Of Jilin University
  • Changsha, China
    • The Third Xiangya Hospital of Central South University
  • Fuzhou, China
    • The First Affiliated Hospital of Fujian Medical University
  • Guangzhou, China
    • Nanfang Hospital Southern Medical University
  • Guangzhou, China
    • The First Affiliated Hospital,Sun Yat-sen University
  • Guiyang, China
    • The Affiliated Hospital of Guizhou Medical University
  • Hangzhou, China
    • the Second Affiliated Hospital Zhejiang University School of Medicine
  • Harbin, China
    • The First Affiliated Hospital of Harbin Medical University
  • Hefei, China
    • The First Affiliated Hospital of Anhui Medical University
  • Hohhot, China
    • Inner Mongolia People's Hospital
  • Jinan, China
    • Qilu Hospital of Shandong University
  • Nanchang, China
    • The Second Affiliated Hospital of Nanchang University
  • Nanjing, China
    • Zhongda Hospital Southeast University
  • Nanjing, China
    • The Affiliated Hospital of Nanjing University Medical School
  • Qingdao, China
    • Qilu Hospital of Shandong University(Qingdao)
  • Shanghai, China
    • Shanghai Jiaotong University School of Medicine Ruijin Hospital
  • Shenyang, China
    • The First Hospital of China Medical University
  • Shijiazhuang, China
    • The Second Hospital of Hebei Medical University
  • Suzhou, China
    • the First Affiliated Hospital of Soochow University
  • Wuhan, China
    • Renmin Hospital of Wuhan University(Hubei General Hospital)
  • Xi'an, China
    • The First Affiliated Hospital Of Xi'an Jiaotong University
  • Zhengzhou, China
    • Henan Provincial People's Hospital
  • Zhengzhou, China
    • the First Affiliated Hospital of Zhengzhou University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 61 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PXT3003; Liquid oral solution, 10 mL twice a day, morning and evening with food	Drug: PXT3003; Patients will be administered PXT3003 twice daily (bid) at 10mL.; Other Names: (RS)-baclofen, naltrexone hydrochloride and D-sorbitol oral fixed dose combination
Placebo Comparator: PXT3003 Placebo; Liquid oral solution, 10 mL twice a day, morning and evening with food	Drug: PXT3003 placebo; Patients will be administered PXT3003 placebo twice daily (bid) at 10mL.; Other Names: liquid oral solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Neuropathy Limitation Scale (ONLS) score	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).	15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment responders rate of PXT3003;	Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment.	15 months
The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS)	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).	15 months
Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2);	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).	15 months
10-Meter Walk Test (10MWT);	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.	15 months
Nine-hole peg test (9HPT) for non-dominant hand ;	The 9-HPT is a simple timed test of fine motor coordination of extremities in the upper limbs.	15 months
Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ;	QMT is used to evaluate motor strength in CMT1A. The following muscles will be evaluated: hand grip (right and left).	15 months
Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side:	The assessment parameters including: Distal motor latency (DML) .	15 months
Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side	The assessment parameters including: Nerve conduction velocity (NCV) .	15 months

Collaborators and Investigators

• Sponsor: Tasly GeneNet Pharmaceuticals Co., Ltd
• Investigators: Study Director: Rui Liu, Tasly Group,Co.Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2021
• Primary Completion (Actual): March 18, 2024
• Study Completion (Actual): March 18, 2024

Study Registration Dates

• First Submitted: September 26, 2021
• First Submitted That Met QC Criteria: October 12, 2021
• First Posted (Actual): October 26, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Gastrointestinal Agents; Sensory System Agents; Neurotransmitter Agents; GABA Agents; Alcohol Deterrents; Neuromuscular Agents; Narcotic Antagonists; Muscle Relaxants, Central; Cathartics; GABA Agonists; GABA-B Receptor Agonists; Naltrexone; Sorbitol; Baclofen
• Other Study ID Numbers: TSL-CM-PXT3003-Ⅲ

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No