Back to resultsPhase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT) (PLEO-CMT)
Primary Purpose
Charcot-Marie-Tooth Disease Type 1A
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
PXT3003 dose 1
PXT3003 dose 2
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Charcot-Marie-Tooth Disease Type 1A focused on measuring PXT3003
Eligibility 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.
Sites / Locations
- Department of Neurology, Cedars-Sinai Medical Center
- Hospital for Special Care, New Britain
- Department of Neurology, McKnight Brain Institute
- University of Kansas Medical Center
- Brigham and Women's Hospital
- University of Michigan Health System
- Department of Neurology, University of Minnesota
- Department of Neurology and Psichiatry, Saint Louis University
- Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
- Ohio State University
- Saint Luke's Rehabilitation Institute
- Departement of Neurology, UZ Leuven
- University Hospital of Quebec
- Centre de Référence des Maladies Neuromusculaires, Hôpital Swynghedauwl, CHU de Lille
- Centre de Référence des Neuropathies Périphériques Rares, Hôpital Dupuytren, CHU Limoges
- Service de Neurologie et du Sommeil, CHU Lyon Sud
- Centre de Référence des Maladies Neuromusculaires, Pôle des Neurosciences Clinique, CHU la Timone
- Centre de Référence des Maladies Neuromusculaires; Hôtel Dieu, CHU de Nantes
- Service de Neurologie, Hôpital Kremlin Bicêtre
- Department of Neurology and Institute for Neuropathology, University Hospital RWTH Aachen
- Department of Clinical Neurophysiology, University Medical Center Göttingen
- Department of Neurology, Ludwig-Maximillian University, Munich
- Department for Sleep Medicine and Neuromuscular, University Hospital Münster
- Departement of Neurology, Academic Medical Center
- Department of neurology, Hospital Univesitario de Bellvitge
- Servicio de Neurologia, Hospital Universitario La Paz
- Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio
- Servicio de Neurologia, Hospital Univesitari i Politécnic La Fe
- Department of Neurology, Salford Royal NHS Foundation Trust
- Ninewells Hospital and Medical School
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Active Comparator
Placebo Comparator
Arm Label
PXT3003 dose 1
PXT3003 dose 2
placebo
Arm Description
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Outcomes
Primary Outcome Measures
Overall Neuropathy Limitation Scale (ONLS) Total Score
The primary efficacy variable used in the main analysis is the mean of the available ONLS values at month 12 and month 15.
The ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score (ODSS) to measure limitations in the everyday activities of the upper limbs (rated on 5 points) and the lower limbs (rated on 7 points). The total score is a 12-point scale: 0 (no disability) to 12 (maximum disability). Lower values in the ONLS indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Secondary Outcome Measures
Mean of Ten Meter Walking Test (10MWT)
This outcome measure is the mean of the available 10MWT values at month 12 and month 15.
The 10MWT is a simple to administer, standardized, reliable and valid evaluation of functional exercise capacity and gait that has been used to evaluate neurologic disorders and CMT patients.
Lower Time to Walk 10 Meters values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Mean of the CMTNS-v2 Sensory Score
This outcome measure is the mean of the available CMTNS-v2 Sensory Score values at month 12 and month 15.
The CMTNS-v2 is a specific scale designed to assess severity of impairment in CMT disease. It is a 36-point scale based on nine items to quantify impairment (sensory symptoms, pin sensibility, vibration and arm and leg strength), activity limitations (motor symptoms arms and legs) and electrophysiological function (amplitudes of ulnar CMAP and SNAP). The CMTNS-v2 goes from 0 (no impairment) to 36 (maximum impairment) whom each sub-items goes from 0 to 4.
The CMTNS-v2 Sensory score is summed of items 1+4+5 of CMTNS-v2 (Sensory symptoms, Pinprick sensibility and Vibration). It is a 12-point score: 0 (no impairment) to 12 (maximum impairment).
Lower CMTNS-v2 Sensory Score values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Mean of the CMTNS-v2 Examination Score (CMTES-v2)
This outcome measure is the mean of the available CMTNS-v2 Examination Score values at month 12 and month 15.
The CMTNS-v2 is a specific scale designed to assess severity of impairment in CMT disease. It is a 36-point scale based on nine items to quantify impairment (sensory symptoms, pin sensibility, vibration and arm and leg strength), activity limitations (motor symptoms arms and legs) and electrophysiological function (amplitudes of ulnar CMAP and SNAP). The CMTNS-v2 goes from 0 (no impairment) to 36 (maximum impairment) whom each sub-items goes from 0 to 4.
The CMTES-v2 is summed of item 1 to 7 of the CMTNS-v2 (limited to impairment items and excluding electrophysiological items). It is a 28-point score: 0 (no impairment) to 28 (maximum impairment).
Lower CMTES-v2 values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Mean of the Results at the Nine-Hole Peg Test (9-HPT)
This outcome measure is the mean of the available 9-HPT values at month 12 and month 15.
The Nine-Hole Peg Test (9HPT) is a simple timed test of fine motor coordination of extremitied in the upper limbs. It measures the time needed by the patient to insert 9 pegs in nine holes and to remove them (normal required time 18 seconds).
Lower 9HPT values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Number of Subjects With at Least One TEAE
Safety selection was to include all randomized patients that have received at least one dose of study treatment.
Safety and tolerability of PXT3003 were compared to placebo on the incidence of treatment-emergent adverse events (TEAEs); they were evaluated by type/nature, severity/intensity, seriousness, and relationship to study drug.
Incidence of AE Leading to Withdrawal of Study Drug
Safety and tolerability of PXT3003 were compared to placebo on the incidence of TEAEs leading to withdrawal of study drug.
Incidence of SAEs
Safety and tolerability of PXT3003 were compared to placebo on the incidence of serious adverse events (SAEs).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02579759
Brief Title
Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)
Acronym
PLEO-CMT
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
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
December 2015 (Actual)
Primary Completion Date
March 2018 (Actual)
Study Completion Date
August 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharnext SA
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
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 limit the production of PMP22 and protect/improve axonal function in patients with CMT1A. On September 18th 2017, PXT3003 dose 2 was prematurely discontinued, due to an unexpected investigational medicinal product quality event (failed month 18 stability testing). This resulted in a large proportion of missing data that led us to reconsider the efficacy analysis that was initially planned in the protocol.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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Charcot-Marie-Tooth Disease Type 1A
Keywords
PXT3003
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
323 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PXT3003 dose 1
Arm Type
Active Comparator
Arm Description
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Arm Title
PXT3003 dose 2
Arm Type
Active Comparator
Arm Description
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months
Intervention Type
Drug
Intervention Name(s)
PXT3003 dose 1
Other Intervention Name(s)
DOSE 1
Intervention Description
Liquid oral solution, 5 ml twice a day, morning and evening with food
Intervention Type
Drug
Intervention Name(s)
PXT3003 dose 2
Other Intervention Name(s)
DOSE 2
Intervention Description
Liquid oral solution, 5 ml twice a day, morning and evening with food
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Liquid oral solution, 5 ml twice a day, morning and evening with food
Primary Outcome Measure Information:
Title
Overall Neuropathy Limitation Scale (ONLS) Total Score
Description
The primary efficacy variable used in the main analysis is the mean of the available ONLS values at month 12 and month 15.
The ONLS is a disability scale that was derived and improved from the Overall Disability Sum Score (ODSS) to measure limitations in the everyday activities of the upper limbs (rated on 5 points) and the lower limbs (rated on 7 points). The total score is a 12-point scale: 0 (no disability) to 12 (maximum disability). Lower values in the ONLS indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Secondary Outcome Measure Information:
Title
Mean of Ten Meter Walking Test (10MWT)
Description
This outcome measure is the mean of the available 10MWT values at month 12 and month 15.
The 10MWT is a simple to administer, standardized, reliable and valid evaluation of functional exercise capacity and gait that has been used to evaluate neurologic disorders and CMT patients.
Lower Time to Walk 10 Meters values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Title
Mean of the CMTNS-v2 Sensory Score
Description
This outcome measure is the mean of the available CMTNS-v2 Sensory Score values at month 12 and month 15.
The CMTNS-v2 is a specific scale designed to assess severity of impairment in CMT disease. It is a 36-point scale based on nine items to quantify impairment (sensory symptoms, pin sensibility, vibration and arm and leg strength), activity limitations (motor symptoms arms and legs) and electrophysiological function (amplitudes of ulnar CMAP and SNAP). The CMTNS-v2 goes from 0 (no impairment) to 36 (maximum impairment) whom each sub-items goes from 0 to 4.
The CMTNS-v2 Sensory score is summed of items 1+4+5 of CMTNS-v2 (Sensory symptoms, Pinprick sensibility and Vibration). It is a 12-point score: 0 (no impairment) to 12 (maximum impairment).
Lower CMTNS-v2 Sensory Score values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Title
Mean of the CMTNS-v2 Examination Score (CMTES-v2)
Description
This outcome measure is the mean of the available CMTNS-v2 Examination Score values at month 12 and month 15.
The CMTNS-v2 is a specific scale designed to assess severity of impairment in CMT disease. It is a 36-point scale based on nine items to quantify impairment (sensory symptoms, pin sensibility, vibration and arm and leg strength), activity limitations (motor symptoms arms and legs) and electrophysiological function (amplitudes of ulnar CMAP and SNAP). The CMTNS-v2 goes from 0 (no impairment) to 36 (maximum impairment) whom each sub-items goes from 0 to 4.
The CMTES-v2 is summed of item 1 to 7 of the CMTNS-v2 (limited to impairment items and excluding electrophysiological items). It is a 28-point score: 0 (no impairment) to 28 (maximum impairment).
Lower CMTES-v2 values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Title
Mean of the Results at the Nine-Hole Peg Test (9-HPT)
Description
This outcome measure is the mean of the available 9-HPT values at month 12 and month 15.
The Nine-Hole Peg Test (9HPT) is a simple timed test of fine motor coordination of extremitied in the upper limbs. It measures the time needed by the patient to insert 9 pegs in nine holes and to remove them (normal required time 18 seconds).
Lower 9HPT values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Title
Number of Subjects With at Least One TEAE
Description
Safety selection was to include all randomized patients that have received at least one dose of study treatment.
Safety and tolerability of PXT3003 were compared to placebo on the incidence of treatment-emergent adverse events (TEAEs); they were evaluated by type/nature, severity/intensity, seriousness, and relationship to study drug.
Time Frame
The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months)
Title
Incidence of AE Leading to Withdrawal of Study Drug
Description
Safety and tolerability of PXT3003 were compared to placebo on the incidence of TEAEs leading to withdrawal of study drug.
Time Frame
The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months)
Title
Incidence of SAEs
Description
Safety and tolerability of PXT3003 were compared to placebo on the incidence of serious adverse events (SAEs).
Time Frame
The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months).
Other Pre-specified Outcome Measures:
Title
Mean of the CMTNS-v2 Sensory Symptoms
Description
This outcome measure is the mean of the available CMTNS-v2 Sensory Symptoms values at month 12 and month 15.
The CMTNS-v2 is a specific scale designed to assess severity of impairment in CMT disease. It is a 36-point scale based on nine items to quantify impairment (sensory symptoms, pin sensibility, vibration and arm and leg strength), activity limitations (motor symptoms arms and legs) and electrophysiological function (amplitudes of ulnar CMAP and SNAP). The CMTNS-v2 goes from 0 (no impairment) to 36 (maximum impairment) whom each sub-items goes from 0 to 4.
The CMTNS-v2 Sensory Symptoms is the first item of the CMTNS-v2. It is a 4-point score: 0 (no impairment) to 4 (maximum impairment).
Lower CMTNS-v2 Sensory Symptoms values indicate a better clinical condition.
Reported values are the values at Baseline (Base) and the average of the available values at Month 12 and Month 15 (Fin).
Time Frame
From Baseline to Month 15
Title
Plasma Concentrations of Baclofen at Trough and at 90 Min After Drug Intake
Description
Plasma concentration of PXT3003 components were measured at trough (prior to dose) and 90 minutes after drug intake.
The mean plasma values of the baseline correspond to half of the administered dose.
Time Frame
At Month 12 and Month 15
Title
Plasma Concentrations of Naltrexone at Trough and at 90 Min After Drug Intake
Description
Plasma concentration of PXT3003 components were measured at trough (prior to dose) and 90 minutes after drug intake.
The mean plasma values of the baseline correspond to half of the administered dose.
Time Frame
At Month 12 and month 15
Title
Plasma Concentrations of 6β-naltrexol at Trough and at 90 Min After Drug Intake
Description
Plasma concentration of PXT3003 components were measured at trough (prior to dose) and peak (90 minutes post dose).
The mean plasma values of the baseline correspond to half of the administered dose.
Time Frame
At Month 12 and Month 15
Title
Number of Participants With ONLS Therapy Response 1
Description
ONLS Therapy Response 1 was defined as the number of participants (responders) with an improvement on final ONLS Total Score of at least one point. A higher response rate indicate a better clinical condition.
Time Frame
From Baseline to Month 15
Title
Number of Participants With ONLS Therapy Response 2
Description
ONLS Therapy Response 2 was defined as the number of participants with no deterioration (responders) on final ONLS Total Score.
A higher response rate indicates a better clinical condition.
Time Frame
From Baseline to Month 15
10. Eligibility
Sex
All
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shahram Attarian, MD
Organizational Affiliation
CHU La Timone, Marseille, France
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Peter Young, MD
Organizational Affiliation
University Hospital Munster, Germany
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Teresa Sevilla, MD
Organizational Affiliation
Hospital Universitari i Politécnic La Fe, Valencia, Spain
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Marianne De Visser, MD
Organizational Affiliation
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Philip Van Damme, MD
Organizational Affiliation
UZ Leuven, Belgium
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Mark Roberts, MD
Organizational Affiliation
Salford Royal NHS Foundation Trust, Manchester, UK
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Florian Thomas, MD
Organizational Affiliation
Saint-Louis University, Saint-Louis, USA
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jack Puymirat, MD
Organizational Affiliation
University Hospital of Quebec
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Cedars-Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Hospital for Special Care, New Britain
City
New Britain
State/Province
Connecticut
ZIP/Postal Code
06053
Country
United States
Facility Name
Department of Neurology, McKnight Brain Institute
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32610
Country
United States
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Health System
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109-5322
Country
United States
Facility Name
Department of Neurology, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
Department of Neurology and Psichiatry, Saint Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104-1027
Country
United States
Facility Name
Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Saint Luke's Rehabilitation Institute
City
Spokane
State/Province
Washington
ZIP/Postal Code
99202-1330
Country
United States
Facility Name
Departement of Neurology, UZ Leuven
City
Leuven
Country
Belgium
Facility Name
University Hospital of Quebec
City
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Centre de Référence des Maladies Neuromusculaires, Hôpital Swynghedauwl, CHU de Lille
City
Lille
Country
France
Facility Name
Centre de Référence des Neuropathies Périphériques Rares, Hôpital Dupuytren, CHU Limoges
City
Limoges
Country
France
Facility Name
Service de Neurologie et du Sommeil, CHU Lyon Sud
City
Lyon
Country
France
Facility Name
Centre de Référence des Maladies Neuromusculaires, Pôle des Neurosciences Clinique, CHU la Timone
City
Marseille
Country
France
Facility Name
Centre de Référence des Maladies Neuromusculaires; Hôtel Dieu, CHU de Nantes
City
Nantes
Country
France
Facility Name
Service de Neurologie, Hôpital Kremlin Bicêtre
City
Paris
Country
France
Facility Name
Department of Neurology and Institute for Neuropathology, University Hospital RWTH Aachen
City
Aachen
Country
Germany
Facility Name
Department of Clinical Neurophysiology, University Medical Center Göttingen
City
Göttingen
Country
Germany
Facility Name
Department of Neurology, Ludwig-Maximillian University, Munich
City
Munich
Country
Germany
Facility Name
Department for Sleep Medicine and Neuromuscular, University Hospital Münster
City
Münster
Country
Germany
Facility Name
Departement of Neurology, Academic Medical Center
City
Amsterdam
Country
Netherlands
Facility Name
Department of neurology, Hospital Univesitario de Bellvitge
City
Barcelona
Country
Spain
Facility Name
Servicio de Neurologia, Hospital Universitario La Paz
City
Madrid
Country
Spain
Facility Name
Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio
City
Sevilla
Country
Spain
Facility Name
Servicio de Neurologia, Hospital Univesitari i Politécnic La Fe
City
Valencia
Country
Spain
Facility Name
Department of Neurology, Salford Royal NHS Foundation Trust
City
Salford
State/Province
Manchester
ZIP/Postal Code
M6 8HD
Country
United Kingdom
Facility Name
Ninewells Hospital and Medical School
City
Dundee
State/Province
Scotland
ZIP/Postal Code
DD1 9SY
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
25519680
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. Erratum In: Orphanet J Rare Dis. 2016;11(1):92.
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PubMed Identifier
25491744
Citation
Chumakov I, Milet A, Cholet N, Primas G, Boucard A, Pereira Y, Graudens E, Mandel J, Laffaire J, Foucquier J, Glibert F, Bertrand V, Nave KA, Sereda MW, Vial E, Guedj M, Hajj R, Nabirotchkin S, Cohen D. Polytherapy with a combination of three repurposed drugs (PXT3003) down-regulates Pmp22 over-expression and improves myelination, axonal and functional parameters in models of CMT1A neuropathy. Orphanet J Rare Dis. 2014 Dec 10;9:201. doi: 10.1186/s13023-014-0201-x.
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result
PubMed Identifier
26070802
Citation
Mandel J, Bertrand V, Lehert P, Attarian S, Magy L, Micallef J, Chumakov I, Scart-Gres C, Guedj M, Cohen D. A meta-analysis of randomized double-blind clinical trials in CMT1A to assess the change from baseline in CMTNS and ONLS scales after one year of treatment. Orphanet J Rare Dis. 2015 Jun 13;10:74. doi: 10.1186/s13023-015-0293-y.
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result
PubMed Identifier
30650121
Citation
Prukop T, Stenzel J, Wernick S, Kungl T, Mroczek M, Adam J, Ewers D, Nabirotchkin S, Nave KA, Hajj R, Cohen D, Sereda MW. Early short-term PXT3003 combinational therapy delays disease onset in a transgenic rat model of Charcot-Marie-Tooth disease 1A (CMT1A). PLoS One. 2019 Jan 16;14(1):e0209752. doi: 10.1371/journal.pone.0209752. eCollection 2019.
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Citation
Hajj R, Prukop T, Wernick S, Ewers D, Brureau A, Cholet N, Laffaire J, Nave KA, Cohen D, Sereda M. Baclofen, Naltrexone and Sorbitol all contribute to the efficacy of PXT3003 in CMT1A Rats. EMJ Neurol, 2019;7[1]:47-49
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result
PubMed Identifier
27387831
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. Erratum to: 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. 2016 Jul 7;11(1):92. doi: 10.1186/s13023-016-0463-6. No abstract available.
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Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/25519680
Description
Attarian et al., 2016
URL
https://www.ncbi.nlm.nih.gov/pubmed/?term=25491744
Description
Chumakov et al., 2014
URL
https://www.ncbi.nlm.nih.gov/pubmed/?term=26070802
Description
Mandel et al., 2015
URL
https://www.ncbi.nlm.nih.gov/pubmed/?term=30650121
Description
Prukop et al., 2019
URL
https://www.ncbi.nlm.nih.gov/pubmed/?term=27387831
Description
Attarian et al., Erratum, 2016
URL
https://www.emjreviews.com/neurology/abstract/baclofen-naltrexone-and-sorbitol-all-contribute-to-the-efficacy-of-pxt3003-in-cmt1a-rats/
Description
Hajj et al., 2019
Learn more about this trial
Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)
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