Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)

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 andable 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 systemicdisease;

• 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 trialcompletion;

• Clinically significant abnormalities on the pre-study laboratory evaluation, physicalevaluation, 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 otherexperimental protocols;

• Patient using unauthorized concomitant treatments including but not limited tobaclofen, naltrexone, sorbitol (pharmaceutical form), opioids, levothyroxin andpotentially neurotoxic drugs such as amiodarone, chloroquine, cancer drugs susceptibleto induce a peripheral neuropathy. Patient who can/agrees to stop these medications 4weeks before randomization and during the whole study duration can be included;

• Female of childbearing potential (apart of patient using adequate contraceptivemeasures), 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, transientvisitors, tourists or any others for whom follow-up evaluation is not assured);

• Limited mental capacity or psychiatric disease rendering the subject unable to providewritten informed consent or comply with evaluation procedures;

• Patient who has participated in another trial of investigational drug(s) within thepast 30 days;

• If a patient from the same family, living in the same household, has already beenincluded in this study, it will not be possible to include another patient from thesame family to avoid mixing of therapeutic units; therefore there would be a risk ofinversion of the blind treatments which could jeopardize the interpretation of studyresults.