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Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01401257
Recruitment Status : Completed
First Posted : July 25, 2011
Results First Posted : February 16, 2017
Last Update Posted : November 22, 2017
Information provided by (Responsible Party):
Pharnext SA

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

Condition or disease Intervention/treatment Phase
Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Genetic Disorders Drug: PXT3003 Low dose Drug: PXT3003 Intermediate Dose Drug: PXT3003 High Dose Other: Placebo Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : December 2010
Actual Primary Completion Date : October 2011
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: PXT3003 Low dose
Oral Liquid formulation, 1/100, bid, 12 months
Drug: PXT3003 Low dose
Liquid,5 ml, twice a day, 12-month treatment
Other Name: Pleocompound PXT3003

Experimental: PXT3003 Intermediate dose
Oral Liquid formulation, 1/50, bid, 12 months
Drug: PXT3003 Intermediate Dose
Liquid,5 ml, twice a day, 12-month treatment
Other Name: Pleocompound PXT3003

Experimental: PXT3003 High dose
Oral Liquid formulation, 1/10, bid, 12 months
Drug: PXT3003 High Dose
Liquid,5 ml, twice a day, 12-month treatment
Other Name: Pleocompound PXT3003

Placebo Comparator: Placebo
Oral Liquid formulation, bid, 12 months
Other: Placebo
Liquid,5 ml, twice a day, 12-month treatment
Other Name: Pleocompound PXT3003

Primary Outcome Measures :
  1. Safety and Tolerability of PXT3003 [ Time Frame: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up ]

    The Primary Objective is to assess the clinical and laboratory safety and tolerability of three doses of PXT3003 administered orally for 12 months to CMT1A patients versus placebo.

    Number of participants with adverse events in each arm.

Secondary Outcome Measures :
  1. To Obtain Preliminary Data on the Efficacy of PXT3003 on Clinical Scores and Functional Tests [ Time Frame: Screening, randomization, 3-, 6-, 9- and 12-months treatment ]

    Efficacy scores and functional tests will be assessed CMTNS/CMTES:ONLS, VAS, fatigue, pain, six minute walk test (6MWT), nine-hole peg test, quantified muscular testing (QMT; hand grip and foot dorsiflexion), CGI.

    For each test or score, change from baseline after 3-,6-, 9- and 12-months of treatment.

  2. To Assess the Pharmacodynamic Effect of PXT3003 on PMP22 mRNA Levels and Intra-epidermal Axon Density in Cutaneous Biopsy [ Time Frame: Randomization and 12-month treatment ]

    A cutaneous biopsy (consisting in 2 small punch biopsies) will be performed to assess PMP22 mRNA expression and intra-epidermal axon density.

    Change from baseline after 12-month of treatment.

  3. To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters [ Time Frame: Screening, randomization, 3-, 6-, 9- and 12-month treatment ]

    Electrophysiological examination will be performed to assess sensory and motor responses of the median and ulnar nerves (non-dominant side) including: NCV, compound muscle action potential (CMAP) and SNAP.

    Change from baseline after 3-,6-, 9- and 12-months of treatment.

  4. To Assess the Pharmacodynamic Effect of PXT3003 on a Series of Biochemical Biomarkers [ Time Frame: Randomization and 3-month treatment ]

    Dosages of biochemical biomarkers in plasma.

    Change from baseline after 3-month of treatment.

  5. To Assess the Plasma Concentrations of PXT3003 [ Time Frame: Randomization, 1-, 6- and 12-month treatment ]
    PXT3003 plasmatic concentrations after one administration (randomization) and after 1-,6-and 12-months of treatment.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01401257

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Hôpital Roger Salengro
Lille, France, 59037
CHU Dupuytren
Limoges, France, 87042
CHU Lyon Sud
Lyon, France, 69495
Hôpital La Timone
Marseille, France, 13385
Hôtel Dieu
Nantes, France, 44093
Groupe Hospitalier Pitié-Salpétrière
Paris, France, 75013
Sponsors and Collaborators
Pharnext SA
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Principal Investigator: Shahram ATTARIAN, MD Hôpital La Timone
Study Director: Viviane BERTRAND, PhD Pharnext SA
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Pharnext SA Identifier: NCT01401257    
Other Study ID Numbers: CLN-PXT3003-01
First Posted: July 25, 2011    Key Record Dates
Results First Posted: February 16, 2017
Last Update Posted: November 22, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Pharnext SA:
Charcot-Marie-Tooth Disease
Hereditary Motor and Sensory Neuropathies
Additional relevant MeSH terms:
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Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Tooth Diseases
Genetic Diseases, Inborn
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities