Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients

  • End date
    Mar 31, 2024
  • participants needed
  • sponsor
    Pharnext SA
Updated on 26 September 2021
Michele Fradkin
Primary Contact
CHU d'Angers, Service de Neurologie (0.7 mi away) Contact
+62 other location


The purpose of this study is to determine whether PXT3003 is effective and safe in the treatment of Charcot-Marie-Tooth disease - Type 1A. This double-blind study will assess in parallel groups 1 dose of PXT3003 compared to Placebo in CMT1A patients treated for 15 months.


This international, multi-center, randomized, double-blind, placebo-controlled, Phase III clinical study is designed to evaluate PXT3003 versus placebo in male and non-pregnant female subjects with genetically confirmed CMT1A of mild-to-moderate severity (CMTNS-V2 score >2 and 18) aged 16 to 65 years.

The study will be conducted in approximately 48 sites worldwide. Genetically confirmed CMT1A subjects will be screened (approximately 500 subjects assuming a 30% screen failure rate) and randomized in a 1:1 ratio to receive either oral PXT3003 daily or matching placebo for 15 months. A total of approximately 350 subjects will be enrolled. Visits will take place at Screening (up to -35 days), Baseline (Day 1), and Months 3, 6, 9, 12, and 15. Randomization will occur at the Baseline (Day 1) Visit. Telephone contacts (TC) will take place at Weeks 2 or 3, Month 1 and 2, and then monthly between subsequent in-person visits. A Safety follow-up visit will be conducted at Month 16.

Subjects will receive in-clinic dosing of study medication at visits on Day 1 and Months 6, 12, and 15. Study medication will be dispensed for outpatient dosing on Day 1 and Months 3, 6, 9, and 12. During outpatient dosing, subjects will complete the Study Medication Diary using an application on their tablet, phone, or computer. The Study Medication Diary will be evaluated, along with returned unused study medication, as part of study drug compliance at visits at Months 3, 6, 9, 12, and 15.

The primary outcome measure (mONLS) and the 10-Meter Walk Test (10mWT), along with the Columbia Suicide Severity Rating Scale (C-SSRS) will be evaluated at each post-Screening visit. The other secondary outcome measures, exploratory outcome, and safety/tolerability assessments will be evaluated as per Schedule of Activities (SOA). A Safety Follow-Up Visit will take place 30 days (Month 16) after the active treatment period ends (Month 15). A Data Safety and Monitoring Board (DSMB) will meet on a scheduled basis throughout the study to review safety data and will reconvene on an ad hoc basis as necessary.

Condition Charcot-Marie-Tooth Disease
Treatment Placebo, (RS)-baclofen, naltrexone hydrochloride and D-sorbitol
Clinical Study IdentifierNCT04762758
SponsorPharnext SA
Last Modified on26 September 2021


Yes No Not Sure

Inclusion Criteria

Male and non-pregnant female subjects, aged 16 to 65 years with a genetically proven diagnosis of CMT1A
Able to provide written informed consent/assent and comply with study procedures
Mild-to-moderate severity assessed by a CMTNS-V2 score >2 and 18
Muscle weakness in at least foot dorsiflexion on clinical assessment
Ulnar nerve motor conduction time of at least 15 m/s
Stable dose of prescribed psychoactive drugs (eg, antidepressants, stimulants, tranquilizers, anti-epileptics) for at least 4 weeks prior to randomization, which is not planned to be changed
Stable dose of prescribed or 'over-the-counter' analgesic medications (eg, paracetamol/acetaminophen, nonsteroidal anti-inflammatory drugs) for at least 2 weeks prior to randomization, which is not planned to be changed
If female, subject must be: (a) surgically sterilized via hysterectomy, bilateral oophorectomy, or bilateral tubal ligation; or (b) of childbearing potential and using a birth control method such as
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation
Progestogen-only hormonal contraception associated with inhibition of ovulation
Intrauterine device
Intrauterine hormone-releasing system
Bilateral tubal occlusion
Vasectomized partner
Sexual abstinence or (c) Of non-childbearing potential (ie, postmenopausal for at least 1 year)
If male, the subject must have had a vasectomy or must use a reliable method of birth control with their partner or total abstinence from sexual intercourse. The subject must agree to continue using their selected method of birth control with their sexual partner during the study and for 120 days after study completion

Exclusion Criteria

Subjects previously enrolled in any PXT3003 study
Subjects living in the same household and enrolled in a PXT3003 study (due to potential lack of adequate storage for study material, risk of mixing treatments and potential unblinding)
CMT of any subtype other than 1A
ONLS score of 0
Known clinically significant motor or sensory abnormalities secondary to a different neurological cause (eg, diabetes, alcohol, vascular, autoimmune, neoplastic, neurodegenerative, human immunodeficiency virus, etc.)
Subjects who have had any surgery or have a concomitant disorder (eg, severe arthrosis) that reduces the mobility of the ankle making it, in the opinion of the investigator, difficult to assess the efficacy of the treatment
Known peripheral neuropathy, myopathy, or neuromuscular disorder of any other kind
Any other clinically significant and/or uncontrolled medical condition that, in the opinion of the investigator, could be a confound or may preclude successful participation or completion of the study
Known hypersensitivity or intolerance to baclofen, naltrexone, or sorbitol
Concomitant treatments including but not limited to baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, and potentially neurotoxic drugs such as amiodarone, chloroquine, and chemotherapeutics capable of inducing peripheral neuropathy. Subjects able to stop these medications at least 2 weeks before randomization and for the study duration may be included
History of porphyria
Diagnosis or history of substance use disorder by Diagnostic and Statistical Manual of Mental Disorders-5th Edition criteria within the past 12 months
Medical or recreational use of marijuana in the 3 months prior to the Screening Visit
Active suicidality (eg, any suicide attempts within the past 12 months or any current suicidal intent, including a plan, as assessed by the C SSRS score of "YES" on questions 4 or 5; and/or based on clinical evaluation by the investigator)
Currently active major depression, as determined by a Beck Depression Inventory-II (BDI-II) score 20
Currently lactating, pregnant, or planning on becoming pregnant during the study
Alanine aminotransferase or aspartate aminotransferase levels greater than 2 times the upper limit of normal
Significant renal impairment as determined by glomerular filtration rate of less than 50 mL/min
Subject has participated in an investigational drug or device study within 30 days prior to the Screening Visit or plans to participate in an investigational drug or device study during the course of this study
Subject is a dependent and/or relative of the Sponsor or Principal Investigator
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