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

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: NCT02579759
Recruitment Status : Completed
First Posted : October 20, 2015
Last Update Posted : October 9, 2018
Information provided by (Responsible Party):
Pharnext SA

Brief Summary:
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 or disease Intervention/treatment Phase
Charcot-Marie-Tooth Disease Type 1A Drug: PXT3003 dose 1 Drug: PXT3003 dose 2 Drug: placebo Phase 3

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. On September 18th 2017, the PXT3003 dose 2 was prematurely discontinued, due to an unexpected investigational medicinal product quality event (failed month 18 stability testing). The independent data safety monitoring committee did not identify any safety concern on September 5th 2017. All patients randomised to dose 2 were requested to undergo the end of study visit, and were offered to enter the extension study (CLN-PXT3003-03).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 323 participants
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
Actual Study Start Date : December 2015
Actual Primary Completion Date : July 2018
Actual Study Completion Date : September 2018

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. 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 :
  1. Responder rate to PXT3003 therapy defined as a patients improving on ONLS at end of treatment [ Time Frame: 15 months of treatment ]
  2. Arm and leg sub-items of ONLS [ Time Frame: 12 and 15 months of treatment ]
  3. Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS-v2), including its sub-items [ Time Frame: 12 and 15 months of treatment ]
  4. Nine-hole Peg Test (9-HPT) performed on non-dominant hand [ Time Frame: 12 and 15 months of treatment ]
  5. Quantified Muscular Testing (QMT) by Hand grip and Foot dorsiflexion dynamometry (mean of both sides) [ Time Frame: 12 and 15 months of treatment ]
  6. Time to walk 10 meters [ Time Frame: 12 and 15 months of treatment ]
  7. Compound Muscle Amplitude Potential (CMAP) in ulnar or median nerves (non-dominant side) [ Time Frame: 12 and 15 months of treatment ]

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

  9. Nerve Conduction Velocity (non-dominant side) [ Time Frame: 12 and 15 months of treatment ]

  10. 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 ]
  11. 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 ]
  12. 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,

Information from the National Library of Medicine

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

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.

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): NCT02579759

  Hide Study Locations
United States, California
Department of Neurology, Cedars-Sinai Medical Center
Los Angeles, California, United States, 90048
United States, Connecticut
Hospital for Special Care, New Britain
New Britain, Connecticut, United States, 06053
United States, Florida
Department of Neurology, McKnight Brain Institute
Gainesville, Florida, United States, 32610
United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Health System
Ann Arbor, Michigan, United States, 48109-5322
United States, Minnesota
Department of Neurology, University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Missouri
Department of Neurology and Psichiatry, Saint Louis University
Saint Louis, Missouri, United States, 63104-1027
United States, New York
Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
New York, New York, United States, 10032
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Washington
Saint Luke's Rehabilitation Institute
Spokane, Washington, United States, 99202-1330
Departement of Neurology, UZ Leuven
Leuven, Belgium
University Hospital of Quebec
Quebec, Canada, G1J 1Z4
Centre de Référence des Maladies Neuromusculaires, Hôpital Swynghedauwl, CHU de Lille
Lille, France
Centre de Référence des Neuropathies Périphériques Rares, Hôpital Dupuytren, CHU Limoges
Limoges, France
Service de Neurologie et du Sommeil, CHU Lyon Sud
Lyon, France
Centre de Référence des Maladies Neuromusculaires, Pôle des Neurosciences Clinique, CHU la Timone
Marseille, France
Centre de Référence des Maladies Neuromusculaires; Hôtel Dieu, CHU de Nantes
Nantes, France
Service de Neurologie, Hôpital Kremlin Bicêtre
Paris, France
Department of Neurology and Institute for Neuropathology, University Hospital RWTH Aachen
Aachen, Germany
Department of Clinical Neurophysiology, University Medical Center Göttingen
Göttingen, Germany
Department of Neurology, Ludwig-Maximillian University, Munich
Munich, Germany
Department for Sleep Medicine and Neuromuscular, University Hospital Münster
Münster, Germany
Departement of Neurology, Academic Medical Center
Amsterdam, Netherlands
Department of neurology, Hospital Univesitario de Bellvitge
Barcelona, Spain
Servicio de Neurologia, Hospital Universitario La Paz
Madrid, Spain
Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio
Sevilla, Spain
Servicio de Neurologia, Hospital Univesitari i Politécnic La Fe
Valencia, Spain
United Kingdom
Department of Neurology, Salford Royal NHS Foundation Trust
Salford, Manchester, United Kingdom, M6 8HD
Ninewells Hospital and Medical School
Dundee, Scotland, United Kingdom, DD1 9SY
Sponsors and Collaborators
Pharnext SA
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

Publications of Results:
Responsible Party: Pharnext SA Identifier: NCT02579759     History of Changes
Other Study ID Numbers: CLN-PXT3003-02
2015-002378-19 ( EudraCT Number )
First Posted: October 20, 2015    Key Record Dates
Last Update Posted: October 9, 2018
Last Verified: October 2018

Keywords provided by Pharnext SA:

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
Peripheral Nervous System Diseases
Neuromuscular Diseases
Congenital Abnormalities
Genetic Diseases, Inborn
Pharmaceutical Solutions