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).
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
187
Liquid oral solution, twice 5 mL (Dose 1) bid
Department of Neurology, Cedars-Sinai Medical Center
Los Angeles, California, United States
Department of Neurology, McKnight Brain Institute
Gainesville, Florida, United States
University of Kansas Medical Center
Kansas City, Kansas, 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
St 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
Departement of Neurology, UZ Leuven
Leuven, Belgium
...and 13 more locations
Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
Incidence of treatment-emergent adverse events (TEAEs) related to PXT3003 during the follow-up in patients with CMT1A
Time frame: 9 or 24 months
Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome
Incidence of all TEAEs and their evaluation of type/nature, severity/intensity, seriousness, duration, relationship to study drug, and outcome
Time frame: 9 or 24 months
Incidence of adverse events leading to withdrawal of study drug
Incidence of adverse events leading to withdrawal of study drug
Time frame: 9 or 24 months
Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items
Overall Neuropathy Limitation Scale (ONLS) score, and its arm and leg sub-items
Time frame: 9 or 24 months
Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items
Charcot-Marie-Tooth Neuropathy Score - version 2 (CMTNS-V2), and its sub-items
Time frame: 9 or 24 months
Nine-hole Peg Test (9-HPT)
Nine-hole Peg Test (9-HPT)
Time frame: 9 or 24 months
Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)
Quantified Muscular Testing (QMT) by hand grip and foot dorsiflexion dynamometry (mean of both sides)
Time frame: 9 or 24 months
Time to walk 10 meters
Time to walk 10 meters
Time frame: 9 or 24 months
Compound Muscle Action Potential (CMAP) on ulnar nerve
Compound Muscle Action Potential (CMAP) on ulnar nerve
Time frame: 9 or 24 months
Sensory Nerve Action Potential (SNAP) on radial nerve
Sensory Nerve Action Potential (SNAP) on radial nerve
Time frame: 9 or 24 months
Nerve conduction velocity (NCV)
Nerve conduction velocity (NCV)
Time frame: 9 or 24 months
Quality of Life (EQ-5D)
Quality of Life (EQ-5D)
Time frame: 9 or 24 months
Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)
Visual analog scale on self-assessment of individualized main impairment in daily activities (defined at baseline with the patient)
Time frame: 9 or 24 months
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