Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
Condition: Charcot-Marie-Tooth Disease; Hereditary Neuropathy With Liability to Pressure Palsies; Genetic Disorders
MeSH terms: Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy; Genetic Diseases, Inborn
Intervention: PXT3003 Low dose; PXT3003 Intermediate Dose; PXT3003 High Dose; Placebo
Intervention description: Liquid,5 ml, twice a day, 12-month treatment; Liquid,5 ml, twice a day, 12-month treatment; Liquid,5 ml, twice a day, 12-month treatment; Liquid,5 ml, twice a day, 12-month treatment
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 80.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: PXT3003; Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathies

Summary:

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

Eligibility criteria:

        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