Clinical trial NCT01401257: Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
Official title: A Phase II, Randomized, Placebo-controlled Trial of the Safety, Efficacy, Pharmacodynamics and Pharmacokinetics of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Charcot-Marie-Tooth Disease
Hereditary Neuropathy With Liability to Pressure Palsies
Genetic Disorders
Keywords: PXT3003
Charcot-Marie-Tooth Disease
Hereditary Motor and Sensory Neuropathies
Lead sponsor: Pharnext S.C.A.
Sponsor class: OTHER
First posted: 2011-07-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed description: In addition to the safety and tolerability of the treatment, clinical, electrophysiological and biological endpoints (PMP22 mRNA, skin biopsy histology and plasma biomarkers) will be assessed. Standard laboratory tests and drug plasma concentrations will also be measured. Because of the slow progression of the disease and the nature of the observed symptoms, a minimum duration of 12 months of treatment is required in order to observe a potential improvement in any of the efficacy parameters.

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

Primary outcomes:
measure: Safety and Tolerability of PXT3003
timeFrame: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up
Secondary outcomes:
measure: To Obtain Preliminary Data on the Efficacy of PXT3003 on Clinical Scores and Functional Tests
timeFrame: Screening, randomization, 3-, 6-, 9- and 12-months treatment
measure: To Assess the Pharmacodynamic Effect of PXT3003 on PMP22 mRNA Levels and Intra-epidermal Axon Density in Cutaneous Biopsy
timeFrame: Randomization and 12-month treatment
measure: To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters
timeFrame: Screening, randomization, 3-, 6-, 9- and 12-month treatment
measure: To Assess the Pharmacodynamic Effect of PXT3003 on a Series of Biochemical Biomarkers
timeFrame: Randomization and 3-month treatment
measure: To Assess the Plasma Concentrations of PXT3003
timeFrame: Randomization, 1-, 6- and 12-month treatment
Other outcomes:
Locations:
city: Lille
country: France
facility: Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: CHU Lyon Sud
city: Marseille
country: France
facility: Hôpital La Timone
city: Nantes
country: France
facility: Hôtel Dieu
city: Paris
country: France
facility: Groupe Hospitalier Pitié-Salpétrière
Study officials:
affiliation: Hôpital La Timone
name: Shahram ATTARIAN, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharnext S.C.A.
name: Viviane BERTRAND, PhD
role: STUDY_DIRECTOR
References:
citation: Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Pereon Y, Dubourg O, Pouget J, Micallef J, Franques J, Lefebvre MN, Ghorab K, Al-Moussawi M, Tiffreau V, Preudhomme M, Magot A, Leclair-Visonneau L, Stojkovic T, Bossi L, Lehert P, Gilbert W, Bertrand V, Mandel J, Milet A, Hajj R, Boudiaf L, Scart-Gres C, Nabirotchkin S, Guedj M, Chumakov I, Cohen D. An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A. Orphanet J Rare Dis. 2014 Dec 18;9:199. doi: 10.1186/s13023-014-0199-0.