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A Phase II, Randomised, Placebo-Controlled Trial of the Safety, Efficacy, Pharmacodynamics of PTX3003 in Patients with Charcot-Marie-Tooth Disease Type 1A - non applicable

Conditions
Charcot-Marie-Tooth disease (type 1A).
MedDRA version: 12.1Level: LLTClassification code 10008414Term: Charcot-Marie-Tooth disease
Registration Number
EUCTR2010-023097-40-FR
Lead Sponsor
Pharnext
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
Authorised-recruitment may be ongoing or finished
Sex
All
Target Recruitment
80
Inclusion Criteria

1. DNA proven CMT1A
2. Muscle weakness in at least foot dorsiflexion (clinical assess-ment)
3. Age between 18 and 65 years
4. Male or non pregnant, non breastfeeding female
5. CMT neuropathy score at screening = 18
6. Agrees to perform neurophysiological studies and two cutaneous biopsies (at baseline and end of treatment) for the determination of PMP22 mRNA expression and histology
7. Providing signed written informed consent to participate in the study and willing and able to comply with all study procedures and scheduled visits.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Patients with another neurological disease
2. Patients using unauthorized concomitant treatments including but not limited to ascorbic acid, opioids, potentially neurotoxic drugs (list provided in appendix 1). Patients who can/agree to stop these medications 4 weeks before randomization can be in-cluded.
3. Patients who have participated in another trial of investigational drug within the past 30 days
4. Concomitant major systemic disease
5. Clinically significant history of unstable medical illness over the last 30 days (unstable angina…)
6. History of significant hematologic, kidney, liver disease, or insu-lin-dependent diabetes
7. Clinically significant abnormalities on the pre-study laboratory evaluation, physical evaluation, ECG
8. ASAT/ALAT and serum creatinin levels above the upper limit of normal (ULN)
9. Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures
10. History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols
11. Female of childbearing potential (apart of patients using ade-quate contraceptive measures), pregnant or breast feeding
12. Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom fol-low-up evaluation is not assured)
13. Limb surgery within six months before randomization or planned before completion of the trial
14. Known allergy to any of the individual components of PXT3003
15. Porphyria (a contra indication to baclofen)

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: To assess the clinical and laboratory safety and tolerability of 3 doses of PXT3003 administered orally for 12 months to CMT1A patients ;Secondary Objective: • To obtain preliminary data on the efficacy of PXT3003 on clini-cal scores and functional tests<br>• To assess the pharmacodynamic effect of PXT3003 in cutaneous biopsy: intra-epidermal axon density and mRNA expression of PMP22<br>• To assess the pharmacodynamic effect of PXT3003 on selected neurophysiological parameters<br>• To assess the pharmacodynamics of PXT3003 on a series of bio-chemical biomarkers <br>• To assess the plasma concentrations (peak and trough) of ba-clofen and naltrexone, two components of PXT3003, in CMT1A patients <br>• To correlate efficacy and safety results with PXT3003 doses<br>;Primary end point(s): Incidence of related Adverse Events (including possibly and probably related AE) with moderate or severe intensity<br><br>
Secondary Outcome Measures
NameTimeMethod
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