Charcot Marie Tooth Type 1A MedDRA version: 20.0 Level: LLT Classification code 10008414 Term: Charcot-Marie-Tooth disease System Organ Class: 100000004850
Conditions
Sponsors
Pharnext SA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male and non-pregnant female subjects, aged 16 to 65 years with a genetically proven diagnosis of CMT1A 2) Able to provide written informed consent/assent and comply with study procedures 3) Mild-to-moderate severity assessed by CMTNS-v2 score >2 and =18 4) Muscle weakness in at least foot dorsiflexion on clinical assessment 5) Ulnar nerve motor conduction time of at least 15m/s 6) Stable dose of prescribed psychoactive drugs (e.g. antidepressants, stimulants, tranquilizers, anti-epileptics) for at least 4 weeks prior to randomization, which is not planned to be changed 7) Stable dose of prescribed or ‘over-the-counter’ (OTC) analgesic medications (e.g. paracetamol/acetaminophen, nonsteroidal anti-inflammatory drugs [NSAIDs]) for at least 2 weeks prior to randomization, which is not planned to be changed 8) 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: o Oral o Intravaginal o Transdermal • Progestogen-only hormonal contraception associated with inhibition of ovulation: o Oral o Injectable o Implantable • Intrauterine device (IUD) • Intrauterine hormone-releasing system (IUS) • Bilateral tubal occlusion • Vasectomized partner • Sexual abstinence; or (c) Of non-childbearing potential (i.e., postmenopausal for at least 1 year) 9) 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. Are the trial subjects under 18? yes Number of subjects for this age range: 56 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 271 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: 1) Subjects previously enrolled in any PXT3003 study 2) 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) 3) CMT of any subtype other than 1A 4) ONLS score of 0 5) Known clinically significant motor or sensory abnormalities secondary to a different neurological cause (e.g. diabetes, alcohol, vascular, autoimmune, neoplastic, neurodegenerative, HIV, etc.) 6) Subjects who have had any surgery or have a concomitant disorder (e.g. 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. 7) Known peripheral neuropathy, myopathy, or neuromuscular disorder of any other kind 8) 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 9) Known hypersensitivity or intolerance to baclofen, naltrexone, or sorbitol 10) 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 11) History of porphyria 12) Diagnosis or history of substance use disorder by DSM-V criteria within the past 12 months 13) Medical or recreational use of marijuana in the 3 months prior to the Screening Visit 14) Active suicidality (e.g. any suicide attempts within the past 12 months or any current suicide intent, including a plan, as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS) score of “YES” on questions 4 or 5; and/or based on clinical evaluation by the investigator) 15) Currently active major depression, as determined by a Beck Depression Inventory (BDI-II) score = 20 16) Currently lactating, pregnant, or planning on becoming pregnant during the study 17) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 2 times the upper limit of normal (ULN) 18) Significant renal impairment as determined by Glomerular Filtration Rate (GFR) of less than 50 mL/min 19) 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 20) Subject is a dependent and/or relative of the Sponsor or investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of treatment with PXT3003 (a fixed-dose combination of (RS)-baclofen, naltrexone hydrochloride, and D-sorbitol) compared to placebo in subjects with CMT1A;Secondary Objective: To evaluate the safety and tolerability of PXT3003 treatment in subjects with CMT1A;Primary end point(s): The change in the modified Overall Neuropathy Limitation Scale (ONLS) between baseline and the Month 15 visit.;Timepoint(s) of evaluation of this end point: Month 15 visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The change from baseline to month 15 in the following outcome measures in hierarchical order: 1) 10-Meter Walk Test (10mWT) 2) Quantified Muscular Testing (bilateral foot dorsiflexion dynamometry) 3) Patient Global Impression of Severity (PGI-S) 4) Patient Global Impression of Change (PGI-C)* 5) Charcot-Marie-Tooth Neuropathy Score, version 2 (CMTNS-v2) 6) Quantified Muscular Testing (hand grip) * Because the PGI-C is already a change assessment, the change from Baseline is not needed for this endpoint.;Timepoint(s) of evaluation of this end point: Month 15 visit | — |
Countries
Belgium, Canada, Denmark, France, Germany, Israel, Italy, Netherlands, Spain, United States
Contacts
Public ContactClinical Operations
Pharnext SA
Outcome results
None listed