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

NCT05092841 | Completed Phase 3

• 1 other identifier: TSL-CM-PXT3003-Ⅲ
• Study Type: interventional
• Target: 176
• Locations: 1 country
• Sites: 25

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.

Conditions

Charcot-Marie-Tooth Type 1A

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Treatment responders rate of PXT3003;

  15 months

• The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS)

  15 months

• Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2);

  15 months

• 10-Meter Walk Test (10MWT);

  15 months

• Nine-hole peg test (9HPT) for non-dominant hand ;

  15 months

Study Arms (2)

PXT3003

EXPERIMENTAL

Liquid oral solution, 10 mL twice a day, morning and evening with food

Drug: PXT3003

PXT3003 Placebo

PLACEBO COMPARATOR

Liquid oral solution, 10 mL twice a day, morning and evening with food

Drug: PXT3003 placebo

Interventions

PXT3003 DRUG

Patients will be administered PXT3003 twice daily (bid) at 10mL.

Also known as: (RS)-baclofen, naltrexone hydrochloride and D-sorbitol oral fixed dose combination

PXT3003

PXT3003 placebo DRUG

Patients will be administered PXT3003 placebo twice daily (bid) at 10mL.

Also known as: liquid oral solution

PXT3003 Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 16 to 65 years (included boundary value), of either sex;
• Patients with CMT1A (PMP22 duplication on chromosome 17p11.2) confirmed by gene diagnosis; 3.2 \< CMTNS-v2 score ≤ 18;
• 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.

You may not qualify if:

• Being allergic to RS-baclofen, naltrexone HCL, D-sorbitol or any component in pxt3003 excipients or having other serious prior allergic reaction;
• Existence contraindications of baclofen, naltrexone or sorbitol, such as porphyria;
• Any other associated cause of peripheral neuropathy such as diabetes mellitus (including diabetes history and glycosylated hemoglobin \>6.5%)
• Subjects with other neurological diseases affecting the evaluation of study treatment;
• Patients with the score of ONLS score is 0;
• 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;
• Limb surgery had implemented within the first six months of randomization or will be planned before the completion of the clinical trial;
• Hepatic or renal dysfunction:
• TBIL\>1.5×ULN,ALT\>3×ULN,AST\>3×ULN;
• Cr\>1.5×ULN;
• Syphilis antibody and HIV antibody positive subjects;
• Subjects with tumors indicated by chest radiograph or B-ultrasound;
• Subjects with alcohol dependence in recent 3 months;
• Females that are of childbearing potential, pregnant, or are breast-feeding;Subjects who are unable to use appropriate contraceptives during the trial;
• 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);

Sponsors & Collaborators

• Tasly GeneNet Pharmaceuticals Co., Ltd: lead

Study Sites (25)

Peking University Third Hospital

Beijing, China

Location

Xuanwu Hospital Capital Medical University

Beijing, China

Location

The First Bethune Hospital of Jilin University

Changchun, China

Location

The Third Xiangya Hospital of Central South University

Changsha, China

Location

The First Affiliated Hospital of Fujian Medical University

Fuzhou, China

Location

Nanfang Hospital Southern Medical University

Guangzhou, China

Location

The First Affiliated Hospital，Sun Yat-sen University

Guangzhou, China

Location

The Affiliated Hospital of Guizhou Medical University

Guiyang, China

Location

The Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, China

Location

The First Affiliated Hospital of Harbin Medical University

Harbin, China

Location

The First Affiliated Hospital of Anhui Medical University

Hefei, China

Location

Inner Mongolia People's Hospital

Hohhot, China

Location

Qilu Hospital of Shandong University

Jinan, China

Location

The Second Affiliated Hospital of Nanchang University

Nanchang, China

Location

The Affiliated Hospital of Nanjing University Medical School

Nanjing, China

Location

Zhongda Hospital Southeast University

Nanjing, China

Location

Qilu Hospital of Shandong University（Qingdao）

Qingdao, China

Location

Shanghai Jiaotong University School of Medicine Ruijin Hospital

Shanghai, China

Location

The First Hospital of China Medical University

Shenyang, China

Location

The Second Hospital of Hebei Medical University

Shijiazhuang, China

Location

The First Affiliated Hospital of Soochow University

Suzhou, China

Location

Renmin Hospital of Wuhan University（Hubei General Hospital）

Wuhan, China

Location

The First Affiliated Hospital of Xi'an Jiaotong University

Xi'an, China

Location

Henan Provincial People's Hospital

Zhengzhou, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, China

Location

MeSH Terms

Interventions

Naltrexone; Sorbitol; Fluid Therapy

Intervention Hierarchy (Ancestors)

Naloxone; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Drug Therapy; Therapeutics

Study Officials

• Rui Liu

  Tasly Group,Co.Ltd.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2021
• First Posted: October 26, 2021
• Study Start: September 28, 2021
• Primary Completion: March 18, 2024
• Study Completion: March 18, 2024
• Last Updated: January 9, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (25)