Charcot-Marie-Tooth disease
Conditions
Interventions
One group will receive two stick-packs with PXT3003 twice daily and the second
group will receive two stick-packs with placebo twice daily.
Sponsors
Pharnext SA
Eligibility
Age
16 Years to 64 Years
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 a 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 15 m/s. 6. If taking prescribed psychoactive drug(s) (eg, antidepressants, stimulants, tranquilizers, anti-epileptics) for CMT1A, should be on a stable dose for at least 4 weeks prior to randomization, which is not planned to be changed. 7. If taking prescribed or *over-the-counter* analgesic medication(s) (eg, paracetamol/acetaminophen, nonsteroidal anti-inflammatory drugs) for CMT1A, should be on a stable dose 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 * Intrauterine hormone-releasing system * Bilateral tubal occlusion * Vasectomized partner * Sexual abstinence or (c) Of non-childbearing potential (ie, no menses for *12 consecutive months without any other underlying medical cause) 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.
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 (eg, diabetes, alcohol, vascular, autoimmune, neoplastic, neurodegenerative, human immunodeficiency virus, etc.). Note: subjects with diagnosis of unilateral carpal tunnel syndrome at least 1 year prior to Screening Visit, that is asymptomatic at the time of Screening Visit, will not be excluded from participating in this study. 6. Subjects who have had any surgery or have a concomitant disorder (eg, severe arthrosis) that reduces the mobility of the ankle or wrist making it, in the opinion of the investigator, difficult to assess the efficacy of the treatment. Note: subjects with surgical repair of unilateral carpal tunnel syndrome will not be excluded from participating in this study. 7. Known peripheral neuropathy, myopathy, or neuromuscular disorder of any other kind. Note: subjects with diagnosis of unilateral carpal tunnel syndrome at least 1 year prior to Screening Visit, that is asymptomatic at the time of Screening Visit, will not be excluded from participating in this study. 8. Any other clinically significant and/or uncontrolled medical condition that, in the opinion of the investigator, could be a confound, may increase subject*s risk, or may preclude successful participation or completion of the study. 9. Known hypersensitivity or intolerance to PXT3003 (or matching placebo), including any of its active ingredients (baclofen, naltrexone, or sorbitol), and/or any of its excipients (acetate buffer, sodium methyl parahydroxybenzoate, sodium propyl parahydroxybenzoate, or isoamyl acetate). 10. Concomitant treatments including but not limited to baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, potent central nervous system depressants (such as barbiturates, long-acting benzodiazepines, and neuroleptics), 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. Subjects with positive urine drug screen at Baseline Visit will be excluded, except for permitted use of codeine and benzodiazepines (see Appendix 2 from the protocol: List of Prohibited Treatments). 11. History of porphyria. 12. Diagnosis or history of substance use disorder by Diagnostic and Statistical Manual of Mental Disorders-5th Edition 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 (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). 15. Currently active major depression, as determined by a Beck Depression Inventory-II (BDI-II) score *20. 16. Currently lactating, pregnant, or planning on becoming pregnant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The change in the modified Overall Neuropathy Limitation Scale (ONLS) between baseline and the Month 15 visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. | — |
Countries
Netherlands
Outcome results
None listed