Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)
Condition: Charcot-Marie-Tooth Disease Type 1A
MeSH terms: Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy; Disease
Intervention: PXT3003 dose 1; PXT3003 dose 2; placebo
Intervention description: Liquid oral solution, 5 ml twice a day, morning and evening with food; Liquid oral solution, 5 ml twice a day, morning and evening with food; Liquid oral solution, 5 ml twice a day, morning and evening with food
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 323.0
Sex: All
Minimum age: 16 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PXT3003

Summary:

      The purpose of this study is to determine whether PXT3003 is effective and safe in the
      treatment of Charcot-Marie-Tooth disease - Type 1 A (CMT1A). This double-blind study will
      assess in parallel groups 2 doses of PXT3003 compared to Placebo in CMT1A patients treated
      for 15 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male or female, aged from 16 to 65 years;

          -  Patient with a proven genetic diagnosis of CMT1A;

          -  Mild-to-moderate severity assessed by Charcot-Marie-Tooth Neuropathy Score (version 2)
             with a score >2 and ≤18;

          -  Muscle weakness in at least foot dorsiflexion;

          -  Motor nerve conduction of the ulnar nerve of at least 15 m/sec;

          -  Providing signed written informed consent to participate in the study and willing and
             able to comply with all study procedures and scheduled visits.

        Exclusion Criteria:

          -  Any other associated cause of peripheral neuropathy such as diabetes;

          -  Patient with another significant neurological disease or a concomitant major systemic
             disease;

          -  Clinically significant history of unstable medical illness since the last 30 days
             (unstable angina, cancer…) that may jeopardize the participation in the study;

          -  Significant hematologic disease, hepatitis or liver failure, renal failure;

          -  Limb surgery within six months before randomization or planned before trial
             completion;

          -  Clinically significant abnormalities on the pre-study laboratory evaluation, physical
             evaluation, electrocardiogram (ECG);

          -  Elevated ASAT/ALAT (> 3 x ULN) and elevated serum creatinine levels (> 1.25 x ULN);

          -  History of recent alcohol or drug abuse or non-adherence with treatment or other
             experimental protocols;

          -  Patient using unauthorized concomitant treatments including but not limited to
             baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, levothyroxin and
             potentially neurotoxic drugs such as amiodarone, chloroquine, cancer drugs susceptible
             to induce a peripheral neuropathy. Patient who can/agrees to stop these medications 4
             weeks before randomization and during the whole study duration can be included;

          -  Female of childbearing potential (apart of patient using adequate contraceptive
             measures), pregnant or breast feeding;

          -  Known hypersensitivity to any of the individual components of PXT3003;

          -  Porphyria as it is a contra indication to baclofen, and it may also induce neuropathy;

          -  Suspected inability to complete the study follow-up (foreign workers, transient
             visitors, tourists or any others for whom follow-up evaluation is not assured);

          -  Limited mental capacity or psychiatric disease rendering the subject unable to provide
             written informed consent or comply with evaluation procedures;

          -  Patient who has participated in another trial of investigational drug(s) within the
             past 30 days;

          -  If a patient from the same family, living in the same household, has already been
             included in this study, it will not be possible to include another patient from the
             same family to avoid mixing of therapeutic units; therefore there would be a risk of
             inversion of the blind treatments which could jeopardize the interpretation of study
             results.