Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients
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.
- 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)
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- 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.
- 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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- UCLA Westwood