Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A

A Phase II, Randomized, Placebo-controlled Trial of the Safety, Efficacy, Pharmacodynamics and Pharmacokinetics of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A.

The present trial is a randomized, placebo-controlled study evaluating 3 different doses of PXT3003 in patients with CMT1A disease.

In addition to the safety and tolerability of the treatment, clinical, electrophysiological and biological endpoints (PMP22 mRNA, skin biopsy histology and plasma biomarkers) will be assessed. Standard laboratory tests and drug plasma concentrations will also be measured. Because of the slow progression of the disease and the nature of the observed symptoms, a minimum duration of 12 months of treatment is required in order to observe a potential improvement in any of the efficacy parameters.

Inclusion Criteria:

• DNA proven CMT1A
• Muscle weakness in at least foot dorsiflexion (clinical assessment)
• Age between 18 and 65 years
• Male or non pregnant, non breastfeeding female
• CMT neuropathy score at screening ≤ 20
• Agrees to perform electrorophysiological studies and two cutaneous biopsies for determination of PMP22 expression and histology
• 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:

• Patients with another neurological disease
• Patients using unauthorized concomitant treatments, ascorbic acid, opioids, levothyroxine and potentially neurotoxic drugs. Patients who can/agree to stop these medications 4 weeks before randomization can be included
• Patients who have participated in another trial of investigational drug within the past 30 days
• Concomitant major systemic disease
• Clinically significant history of unstable medical illness over the last 30 days (unstable angina…)
• History of significant hematologic, kidney, liver disease, or insulin-dependent diabetes
• Clinically significant abnormalities on the prestudy laboratory evaluation, physical evaluation, electrocardiogram (ECG)
• ASAT/ALAT levels above the upper limit of normal (ULN). However, patients with an isolated elevation of either ASAT or ALAT (<1.5 ULN) can be included at investigators" discretion if the remaining liver function tests are normal and if ASAT or ALAT value is stable at 2 distinct evaluations in the month prior to inclusion
• Serum creatinine levels above the upper limit of normal
• Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures
• History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols
• Female of childbearing potential (apart of patient using adequate contraceptive measures), pregnant or breast feeding
• Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom follow-up evaluation is not assured)
• Limb surgery in the six months before randomization or planned before completion of the trial
• Known hypersensitivity to any of the individual components of PXT3003
• Porphyria