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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

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

Detailed Summary: 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.
Sponsor: Pharnext SA

Current Primary Outcome: 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.



Original Primary Outcome: Same as current

Current Secondary Outcome:

  • 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.

  • 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.

  • 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.

  • 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.

  • 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.


Original Secondary Outcome: Same as current

Information By: Pharnext SA

Dates:
Date Received: July 20, 2011
Date Started: December 2010
Date Completion:
Last Updated: December 23, 2016
Last Verified: July 2011