Assessing Long Term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A
- Conditions
- Charcot-Marie-Tooth Disease, Type IA
- Interventions
- Registration Number
- NCT03023540
- Lead Sponsor
- Pharnext S.C.A.
- Brief Summary
All randomised patients with Charcot-Marie-Tooth Type 1A (CMT1A) who completed the primary study CLN-PXT3003-02, i.e. treatment with PXT3003 or placebo, are eligible to continue in the extension study CLN-PXT3003-03.
Period 1: Patients randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL).
Period 2: All patients continue on twice dose 1 (2X5mL).
- Detailed Description
PXT3003 is a rational design, fixed combination of low-dose (RS) baclofen, naltrexone hydrochloride and D-sorbitol. The use of PXT3003 in a multicenter, randomised, placebo controlled phase II study (CLN-PXT3003-01) was well-tolerated and safe in patients with CMT1A for the three dose-levels investigated (Attarian et al., 2014). The intermediate and high dose of PXT3003 demonstrated an improvement of disability in this patient population.
Subsequently a multicenter, randomised, placebo controlled phase III study (CLN-PXT3003-02) to assess the efficacy and safety of PXT3003 in the treatment of patients with CMT1A was initiated in December 2015. In March 2017 the first patients completed the 15-month treatment with PXT3003 and rolled over into the extension study CLN-PXT3003-03.
During Period 1 (9 months), patients that were randomised to PXT3003 dose 1 or placebo in the primary study (CLN-PXT3003-02) continued in the extension study on PXT3003 dose 1 (5 mL). Patients randomised to PXT3003 dose 2 (5 mL) in the primary study (CLN-PXT3003-02) continued in the extension study on on PXT3003 dose 2 or PXT3003 twice dose 1 (2x5 mL). During Period 2, all patients continue on twice dose 1 (2X5mL).
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 187
Not provided
- Any clinically significant change in health status that, in the opinion of the Investigator, would prevent the subject from participating in this study or successfully completing this study
- Any unauthorized concomitant treatments, as study CLN-PXT3003-02 (e.g. 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 peripheral neuropathy)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PXT3003 dose 2 PXT3003 Period 1, PXT3003: Liquid oral solution (1.2 mg/mL baclofen, 0.14 mg/mL naltrexone HCl and 420 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months Period 2, PXT3003: Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 10 mL bid (taken morning and evening with food) PXT3003 dose 1 PXT3003 Period 1, PXT3003 : Liquid oral solution (0.6 mg/mL baclofen, 0.07 mg/mL naltrexone HCl and 210 mg/mL D-sorbitol), 5 mL bid (taken morning and evening with food) for 9 consecutive months
- Primary Outcome Measures
Name Time Method Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A 9 or 24 months Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
- Secondary Outcome Measures
Name Time Method Incidence of adverse events leading to withdrawal of study drug 9 or 24 months Incidence of adverse events leading to withdrawal of study drug
Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items 9 or 24 months Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items
Time to walk 10 meters 9 or 24 months Time to walk 10 meters
Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome 9 or 24 months Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome
Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items 9 or 24 months Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items
Nine-hole Peg Test (9-HPT) 9 or 24 months Nine-hole Peg Test (9-HPT)
Compound Muscle Action Potential (CMAP) on ulnar nerve 9 or 24 months Compound Muscle Action Potential (CMAP) on ulnar nerve
Nerve conduction velocity (NCV) 9 or 24 months Nerve conduction velocity (NCV)
Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient) 9 or 24 months Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)
Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides) 9 or 24 months Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)
Sensory Nerve Action Potential (SNAP) on radial nerve 9 or 24 months Sensory Nerve Action Potential (SNAP) on radial nerve
Quality of Life (EQ-5D) 9 or 24 months Quality of Life (EQ-5D)
Trial Locations
- Locations (23)
Departement of Neurology, UZ Leuven
🇧🇪Leuven, Belgium
Servicio de Neurologia, Hospital Universitario i Politécnic La Fe
🇪🇸Valencia, Spain
Department of Neurology, Salford Royal NHS Foundation Trust
🇬🇧Salford, Manchester, United Kingdom
Department of Neurology, McKnight Brain Institute
🇺🇸Gainesville, Florida, United States
Department of Neurology, Cedars-Sinai Medical Center
🇺🇸Los Angeles, California, United States
Brigham and Women's Hospital
🇺🇸Boston, Massachusetts, United States
University of Michigan Health System
🇺🇸Ann Arbor, Michigan, United States
Department of Neurology, University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Department of Neurology and Psichiatry, Saint Louis University
🇺🇸Saint Louis, Missouri, United States
Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
🇺🇸New York, New York, United States
Saint Luke's Rehabilitation Institute
🇺🇸Spokane, Washington, United States
University Hospital of Quebec
🇨🇦Quebec, Canada
Cntre de Reference des Maladies Neuromusculaires, Hopital Swynghedauwl, CHU Lille
🇫🇷Lille, France
Service de Neurologie et du Sommeil, CHU Lyon Sud
🇫🇷Lyon, France
Centre de Reference des Maladie Neuromusculaires, CHU la Timone
🇫🇷Marseille, France
Centre de Reference des Maladie Neuromusculaires, Hotel Dieu, CHU de Nantes
🇫🇷Nantes, France
Service de Neurologie, Hopital Kremlin Bicetre
🇫🇷Paris, France
Departement of Neurology, Academic Medical Center
🇳🇱Amsterdam, Netherlands
Department of neurology, Hospital Univesitario de Bellvitge
🇪🇸Barcelona, Spain
Servicio de Neurologia, Hospital Universitario La Paz
🇪🇸Madrid, Spain
Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain
Centre de Reference des Neuropathies Peripheriques Rare, Hopital Dupuytren, CHU Limoges
🇫🇷Limoges, France
University of Kansas Medical Center
🇺🇸Kansas City, Kansas, United States