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Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT) (PLEO-CMT)

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT02579759
First Posted: October 20, 2015
Last Update Posted: January 5, 2017
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.
Information provided by (Responsible Party):
Pharnext SA
  Purpose
The purpose of this study is to determine whether PXT3003 is effective and safe in the treatment of Charcot-Marie-Tooth disease - Type 1 A (CMT1A). This double-blind study will assess in parallel groups 2 doses of PXT3003 compared to Placebo in CMT1A patients treated for 15 months.

Condition Intervention Phase
Charcot-Marie-Tooth Disease Type 1A Drug: PXT3003 dose 1 Drug: PXT3003 dose 2 Drug: placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: International, Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Study Assessing in Parallel Groups the Efficacy and Safety of 2 Doses of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A Treated 15 Months

Resource links provided by NLM:


Further study details as provided by Pharnext SA:

Primary Outcome Measures:
  • Disability measured by the change in the Overall Neuropathy Limitation Scale (ONLS) score [ Time Frame: 12 and 15 months of treatment ]
    Analysis of Covariance on the summary mean of ONLS at 12 and 15 months adjusted for baseline ONLS values.


Secondary Outcome Measures:
  • Responder rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment [ Time Frame: 15 months of treatment ]
  • Arm and leg sub-items of ONLS [ Time Frame: 12 and 15 months of treatment ]
  • Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS-v2), including its sub-items [ Time Frame: 12 and 15 months of treatment ]
  • Nine-hole Peg Test (9-HPT) performed on non-dominant hand [ Time Frame: 12 and 15 months of treatment ]
  • Quantified Muscular Testing (QMT) by Hand grip and Foot dorsiflexion dynamometry (mean of both sides) [ Time Frame: 12 and 15 months of treatment ]
  • Time to walk 10 meters [ Time Frame: 12 and 15 months of treatment ]
  • Compound Muscle Amplitude Potential (CMAP) in ulnar or median nerves (non-dominant side) [ Time Frame: 12 and 15 months of treatment ]
    mV

  • Sensory Nerve Potential Amplitude (SNAP) in radial nerve (non-dominant side) [ Time Frame: 12 and 15 months of treatment ]
    µV

  • Nerve Conduction Velocity (non-dominant side) [ Time Frame: 12 and 15 months of treatment ]
    m/sec

  • Quality of life measured by the EuroQol 5-Dimensional Health-related Quality of Life scale (EQ-5D-L) [ Time Frame: 12 and 15 months of treatment ]
  • visual analog scale on self-assessment of the individualized main impairment in daily activities defined at baseline with the patient [ Time Frame: 12 and 15 months of treatment ]
  • Safety and tolerability of PXT3003: assessment of some AE incidence and of the change in physical examination, vital signs, clinical laboratory variables, and ECGs. [ Time Frame: 15 months of treatment ]
    Incidence of Treatment Emergent Adverse Events (TEAE), of related TEAE with moderate or severe intensity, AE leading to withdrawal of study drug, and Serious Adverse Events,


Enrollment: 323
Study Start Date: December 2015
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: PXT3003 dose 1
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Drug: PXT3003 dose 1
Liquid oral solution, 5 ml twice a day, morning and evening with food
Active Comparator: PXT3003 dose 2
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Drug: PXT3003 dose 2
Liquid oral solution, 5 ml twice a day, morning and evening with food
Placebo Comparator: placebo
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Drug: placebo
Liquid oral solution, 5 ml twice a day, morning and evening with food

Detailed Description:
PXT3003, is a fixed dose combination of (RS)-baclofen, naltrexone hydrochloride and D-sorbitol selected via a Systems Biology approach and developed by Pharnext, with the aim to lower toxic PMP22 gene over-expression in CMT1A.
  Eligibility

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.


Ages Eligible for Study:   16 Years to 65 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female, aged from 16 to 65 years;
  • Patient with a proven genetic diagnosis of CMT1A;
  • Mild-to-moderate severity assessed by Charcot-Marie-Tooth Neuropathy Score (version 2) with a score >2 and ≤18;
  • Muscle weakness in at least foot dorsiflexion;
  • Motor nerve conduction of the ulnar nerve of at least 15 m/sec;
  • 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:

  • Any other associated cause of peripheral neuropathy such as diabetes;
  • Patient with another significant neurological disease or a concomitant major systemic disease;
  • Clinically significant history of unstable medical illness since the last 30 days (unstable angina, cancer…) that may jeopardize the participation in the study;
  • Significant hematologic disease, hepatitis or liver failure, renal failure;
  • Limb surgery within six months before randomization or planned before trial completion;
  • Clinically significant abnormalities on the pre-study laboratory evaluation, physical evaluation, electrocardiogram (ECG);
  • Elevated ASAT/ALAT (> 3 x ULN) and elevated serum creatinine levels (> 1.25 x ULN);
  • History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols;
  • Patient using unauthorized concomitant treatments 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 a peripheral neuropathy. Patient who can/agrees to stop these medications 4 weeks before randomization and during the whole study duration can be included;
  • Female of childbearing potential (apart of patient using adequate contraceptive measures), pregnant or breast feeding;
  • Known hypersensitivity to any of the individual components of PXT3003;
  • Porphyria as it is a contra indication to baclofen, and it may also induce neuropathy;
  • Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom follow-up evaluation is not assured);
  • Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures;
  • Patient who has participated in another trial of investigational drug(s) within the past 30 days;
  • If a patient from the same family, living in the same household, has already been included in this study, it will not be possible to include another patient from the same family to avoid mixing of therapeutic units; therefore there would be a risk of inversion of the blind treatments which could jeopardize the interpretation of study results.
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT02579759


  Show 30 Study Locations
Sponsors and Collaborators
Pharnext SA
Investigators
Principal Investigator: Shahram Attarian, MD CHU La Timone, Marseille, France
Principal Investigator: Peter Young, MD University Hospital Munster, Germany
Principal Investigator: Teresa Sevilla, MD Hospital Universitari i Politécnic La Fe, Valencia, Spain
Principal Investigator: Marianne De Visser, MD Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Principal Investigator: Philip Van Damme, MD UZ Leuven, Belgium
Principal Investigator: Mark Roberts, MD Salford Royal NHS Foundation Trust, Manchester, UK
Principal Investigator: Florian Thomas, MD Saint-Louis University, Saint-Louis, USA
  More Information

Publications:
Responsible Party: Pharnext SA
ClinicalTrials.gov Identifier: NCT02579759     History of Changes
Other Study ID Numbers: CLN-PXT3003-02
2015-002378-19 ( EudraCT Number )
First Submitted: September 28, 2015
First Posted: October 20, 2015
Last Update Posted: January 5, 2017
Last Verified: January 2017

Keywords provided by Pharnext SA:
PXT3003

Additional relevant MeSH terms:
Tooth Diseases
Charcot-Marie-Tooth Disease
Nerve Compression Syndromes
Hereditary Sensory and Motor Neuropathy
Stomatognathic Diseases
Nervous System Malformations
Nervous System Diseases
Heredodegenerative Disorders, Nervous System
Neurodegenerative Diseases
Polyneuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Pharmaceutical Solutions