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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05092841
Recruitment Status : Recruiting
First Posted : October 26, 2021
Last Update Posted : March 2, 2022
Sponsor:
Information provided by (Responsible Party):
Tasly Pharmaceutical Group Co., Ltd ( Tasly GeneNet Pharmaceuticals Co., Ltd )

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.

Condition or disease Intervention/treatment Phase
Charcot-Marie-Tooth Type 1A Drug: PXT3003 Drug: PXT3003 placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 176 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : September 28, 2021
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : December 30, 2023


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 Name: (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 Name: liquid oral solution




Primary Outcome Measures :
  1. Overall Neuropathy Limitation Scale (ONLS) score [ Time Frame: 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 Outcome Measures :
  1. Treatment responders rate of PXT3003; [ Time Frame: 15 months ]
    Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment.

  2. The sub-item of Arm and leg scores in Overall Neuropathy Limitation Scale (ONLS) [ Time Frame: 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).

  3. Total and sub-item score of Charcot-Marie-Tooth neuropathy score second version (CMTNS-V2); [ Time Frame: 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).

  4. 10-Meter Walk Test (10MWT); [ Time Frame: 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.

  5. Nine-hole peg test (9HPT) for non-dominant hand ; [ Time Frame: 15 months ]
    The 9-HPT is a simple timed test of fine motor coordination of extremities in the upper limbs.

  6. Quantified Muscular Testing (QMT) (grip strength and bilateral foot dorsiflexion dynamometry) ; [ Time Frame: 15 months ]
    QMT is used to evaluate motor strength in CMT1A. The following muscles will be evaluated: hand grip (right and left).

  7. Electrophysiological parameters Sensory responses measured at ulnar and radial nerves on the non-dominant side: [ Time Frame: 15 months ]
    The assessment parameters including: Distal motor latency (DML) .

  8. Electrophysiological parameters motor responses measured at ulnar and radial nerves on the non-dominant side [ Time Frame: 15 months ]
    The assessment parameters including: Nerve conduction velocity (NCV) .



Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05092841


Contacts
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Contact: Rui Liu 022-86343626 liurui2@tasly.com

Locations
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Sponsors and Collaborators
Tasly GeneNet Pharmaceuticals Co., Ltd
Investigators
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Study Director: Rui Liu Tasly Group,Co.Ltd.
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Responsible Party: Tasly GeneNet Pharmaceuticals Co., Ltd
ClinicalTrials.gov Identifier: NCT05092841    
Other Study ID Numbers: TSL-CM-PXT3003-Ⅲ
First Posted: October 26, 2021    Key Record Dates
Last Update Posted: March 2, 2022
Last Verified: February 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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