Charcot-Marie-Tooth Disease - Type 1A MedDRA version: 20.0 Level: LLT Classification code 10008414 Term: Charcot-Marie-Tooth disease System Organ Class: 100000004850
Conditions
Interventions
Product Code: PXT3003 dose 1
Pharmaceutical Form: Oral solution
INN or Proposed INN: RS-BACLOFEN
CAS Number: 1134-47-0
Concentration uni
Sponsors
PHARNEXT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female, aged from 16 to 65 years; 2. Patient with a proven genetic diagnosis of CMT1A; 3. Mild-to-moderate severity assessed by CMTNS-v2 with a score >2 and =18; 4. Muscle weakness in at least foot dorsiflexion; 5. Motor nerve conduction of the ulnar nerve of at least 15m/sec; 6. 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? yes Number of subjects for this age range: 30 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 270 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Any other associated cause of peripheral neuropathy such as diabetes; 2. Patients with another significant neurological disease or a concomitant major systemic disease; 3. Clinically significant history of unstable medical illness since the last 30 days (unstable angina, cancer…) that may jeopardize the participation in the study; 4. Significant hematologic disease, hepatitis or liver failure, renal failure; 5. Limb surgery within six months before randomization or planned before trial completion; 6. Clinically significant abnormalities on the pre-study laboratory evaluation, physical evaluation, electrocardiogram (ECG); 7. Elevated ASAT/ALAT (> 3 x ULN) and elevated serum creatinine levels (> 1.25 x ULN); 8. History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols; 9. Patients 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; (list provided in appendix 1). Patients who can/agree to stop these medications 4 weeks before randomization and during the whole study duration can be included; 10. Female of childbearing potential (apart of patients using adequate contraceptive measures), pregnant or breast feeding; 11. Known hypersensitivity to any of the individual components of PXT3003; 12. Porphyria as it is a contra indication to baclofen, and it may also induce neuropathy; 13. Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom follow-up evaluation is not assured); 14. Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures; 15. Patients who have participated in another trial of investigational drug(s) within the past 30 days; 16. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of PXT3003 compared to Placebo on the disability measured by the ONLS score in CMT1A patients treated for 15 months.; Secondary Objective: - To assess the efficacy of PXT3003 compared to Placebo on clinical score and functional tests, electrophysiological parameters, and measures of quality of life; - To assess the safety and tolerability of PXT3003 compared to Placebo; - To assess plasma concentrations of PXT3003 components (at peak and trough) when administered with 2 different doses; - To assess the change over time of potential blood biomarkers; - To assess molecular changes in skin biopsy, when this procedure will be possible (ancillary sub-study); - To explore potential new imaging biomarkers by leg MRI, when this procedure will be possible (ancillary sub-study) ;Primary end point(s): Improvement of disability measured by the Overall Neuropathy Limitation Scale (ONLS) score.;Timepoint(s) of evaluation of this end point: Baseline (V1) ; 12 and 15 months of treatment (V5 and V6) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints - Responders Rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment; - The effect of the studied PXT3003 dosages on the following endpoints: *Arm and leg sub-items of ONLS; *Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS-v2), including its sub-items; *Nine-hole Peg Test (9-HPT) performed on non-dominant hand; *Quantified Muscular Testing (QMT) by Hand grip and Foot dorsiflexion dynamometry (mean of both sides); *Time to walk 10 meters; *Electrophysiological parameters assessing sensory and motor responses of ulnar and radial nerves (non-dominant side) including: o Compound Muscle Action Potential (CMAP) on ulnar nerve; o Sensory Nerve Action Potential (SNAP) on radial nerve; o Nerve conduction velocity (NCV); * Quality of life measured by: o EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D); o VAS on self-assessment of the individualized main impairment in daily activities defined at baseline with the patient. Secondary safety endpoints Safety and tolerability of PXT3003 will be compared to placebo on the following parameters: - Incidence of all Treatment Emergent Adverse Events (TEAEs); they will be evaluated by type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome; - Incidence of related TEAEs (including possibly and probably related TEAEs) with a moderate or severe intensity; - Incidence of AE leading to withdrawal of study drug; - Incidence of Serious Adverse Events (SAEs); - Change in physical examination, vital signs (blood pressure and heart rate), 12-lead ECG, and laboratory data ( | — |
Countries
Belgium, France, Germany, Netherlands, United Kingdom, United States
Contacts
Public ContactAgnes Daoust
PHARNEXT
Outcome results
None listed