Charcot-Marie-Tooth Disease Type 1APhase 3PLEO-CMTNCT02579759
Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)
A Phase 3 study testing PXT3003 dose 1 and PXT3003 dose 2 in people with Charcot-Marie-Tooth Disease Type 1A, run by Pharnext S.C.A. at 30 sites in 8 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 65 years
- Conditions the study is for
- Charcot-Marie-Tooth Disease Type 1A
- What is being tested?
- PXT3003 dose 1 and PXT3003 dose 2
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 323 participants
- Where
- 30 sitesin 8 countries
- Study dates
- Dec 2015to Aug 2018
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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);
Show all 16Show fewer
- 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.
Trial locations and contacts
30 sites in 8 countries.
30 sites in 8 countries
United States11 sites
University of Michigan Health System
Ann Arbor, Michigan, 48109-5322
Brigham and Women's Hospital
Boston, Massachusetts, 02115
Ohio State University
Columbus, Ohio, 43210
Department of Neurology, McKnight Brain Institute
Gainesville, Florida, 32610
University of Kansas Medical Center
Kansas City, Kansas, 66160
Department of Neurology, Cedars-Sinai Medical Center
Los Angeles, California, 90048
Department of Neurology, University of Minnesota
Minneapolis, Minnesota, 55455
Hospital for Special Care, New Britain
New Britain, Connecticut, 06053
Peripheral Neuropathy Center, Neurological Institue Building, Columbia University Medical Center
New York, New York, 10032
Saint Luke's Rehabilitation Institute
Spokane, Washington, 99202-1330
Department of Neurology and Psichiatry, Saint Louis University
St Louis, Missouri, 63104-1027
France6 sites
Centre de Référence des Maladies Neuromusculaires, Hôpital Swynghedauwl, CHU de Lille
Lille
Centre de Référence des Neuropathies Périphériques Rares, Hôpital Dupuytren, CHU Limoges
Limoges
Service de Neurologie et du Sommeil, CHU Lyon Sud
Lyon
Centre de Référence des Maladies Neuromusculaires, Pôle des Neurosciences Clinique, CHU la Timone
Marseille
Centre de Référence des Maladies Neuromusculaires; Hôtel Dieu, CHU de Nantes
Nantes
Service de Neurologie, Hôpital Kremlin Bicêtre
Paris
Germany4 sites
Department of Neurology and Institute for Neuropathology, University Hospital RWTH Aachen
Aachen
Department of Clinical Neurophysiology, University Medical Center Göttingen
Göttingen
Department of Neurology, Ludwig-Maximillian University, Munich
Munich
Department for Sleep Medicine and Neuromuscular, University Hospital Münster
Münster
Spain4 sites
Department of neurology, Hospital Univesitario de Bellvitge
Barcelona
Servicio de Neurologia, Hospital Universitario La Paz
Madrid
Centro de Diagnostico y Tratamiento, Hospital Universitario Virgen del Rocio
Seville
Servicio de Neurologia, Hospital Univesitari i Politécnic La Fe
Valencia
United Kingdom2 sites
Ninewells Hospital and Medical School
Dundee, Scotland, DD1 9SY
Department of Neurology, Salford Royal NHS Foundation Trust
Salford, Manchester, M6 8HD
Netherlands1 site
Departement of Neurology, Academic Medical Center
Amsterdam
About this study
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
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.
Read the 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).
- Conditions
- Charcot-Marie-Tooth Disease Type 1A
- Being tested
- PXT3003 dose 1, PXT3003 dose 2, placebo
- Keywords
- PXT3003
- Medical subject headings
- Charcot-Marie-Tooth Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PXT3003 dose 1Drug
Also called DOSE 1
Liquid oral solution, 5 ml twice a day, morning and evening with food
PXT3003 dose 2Drug
Also called DOSE 2
Liquid oral solution, 5 ml twice a day, morning and evening with food
placeboDrug
Liquid oral solution, 5 ml twice a day, morning and evening with food
| Study group | Role | What they receive |
|---|---|---|
| PXT3003 dose 1 | Active comparator | Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months Receives: Drug: PXT3003 dose 1 |
| PXT3003 dose 2 | Active comparator | Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months Receives: Drug: PXT3003 dose 2 |
| placebo | Placebo comparator | Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: From Baseline to Month 15
Secondary outcomes (7)
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).
Measured: From Baseline to Month 15
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).
Measured: From Baseline to Month 15
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).
Measured: From Baseline to Month 15
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).
Measured: From Baseline to Month 15
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.
Measured: 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)
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.
Measured: 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)
Incidence of SAEs
Safety and tolerability of PXT3003 were compared to placebo on the incidence of serious adverse events (SAEs).
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Oct 2015 (estimated)
- Study startDec 2015
- Primary completionMar 2018
- Study completionAug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Charcot-Marie-Tooth Disease Type 1AStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 323 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pharnext S.C.A.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shahram Attarian, MD, Principal investigator, CHU La Timone, Marseille, FrancePeter Young, MD, Principal investigator, University Hospital Munster, GermanyTeresa Sevilla, MD, Principal investigator, Hospital Universitari i Politécnic La Fe, Valencia, SpainMarianne De Visser, MD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Philip Van Damme, MD, Principal investigator, UZ Leuven, BelgiumMark Roberts, MD, Principal investigator, Salford Royal NHS Foundation Trust, Manchester, UKFlorian Thomas, MD, Principal investigator, Saint-Louis University, Saint-Louis, USAJack Puymirat, MD, Principal investigator, University Hospital of Quebec
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02579759
- Sponsor's protocol ID
- CLN-PXT3003-02
- Other IDs
- 2015-002378-19, 2015
- Acronym
- PLEO-CMT
- Status last verified
- Feb 2020
- First submitted
- 28 Sep 2015
- Last updated
- 27 Feb 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 25519680Chumakov 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.
PubMed 25491744Mandel 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.
PubMed 26070802Prukop 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.
PubMed 30650121Hajj 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
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.
PubMed 27387831
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02579759
- Acronym / sponsor ID
- PLEO-CMT / CLN-PXT3003-02
- Conditions
- Charcot-Marie-Tooth Disease Type 1A
- Keywords
- PXT3003
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 323 participants (actual)
- Lead sponsor
- Pharnext S.C.A.University, hospital or other
- Study start
- Dec 2015 (actual)
- Primary completion
- Mar 2018 (actual)
- Study completion
- Aug 2018 (actual)
- First posted
- 20 Oct 2015 (estimated)
- Results
- Posted 27 Feb 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PXT3003 dose 1 | Active comparator | Drug: PXT3003 dose 1Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months |
| PXT3003 dose 2 | Active comparator | Drug: PXT3003 dose 2Oral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months |
| placebo | Placebo comparator | Drug: placeboOral solution, 5 ml b.i.d. (taken morning and evening with food) during 15 months |
Who may qualify
- Ages
- 16 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (16 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PXT3003 dose 1Also: DOSE 1Liquid oral solution, 5 ml twice a day, morning and evening with food | Drug | PXT3003 dose 1 |
| PXT3003 dose 2Also: DOSE 2Liquid oral solution, 5 ml twice a day, morning and evening with food | Drug | PXT3003 dose 2 |
| placeboLiquid oral solution, 5 ml twice a day, morning and evening with food | Drug | placebo |
Primary outcome
Overall Neuropathy Limitation Scale (ONLS) Total Score
Time frame: From Baseline to Month 15
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).
7 secondary outcomes
Mean of Ten Meter Walking Test (10MWT)
Time frame: From Baseline to Month 15
Mean of the CMTNS-v2 Sensory Score
Time frame: From Baseline to Month 15
Mean of the CMTNS-v2 Examination Score (CMTES-v2)
Time frame: From Baseline to Month 15
Mean of the Results at the Nine-Hole Peg Test (9-HPT)
Time frame: From Baseline to Month 15
Number of Subjects With at Least One TEAE
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)
Incidence of AE 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)
Incidence of 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).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25519680Attarian 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.
- Results publication: PubMed 25491744Chumakov 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.
- Results publication: PubMed 26070802Mandel 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.
- Results publication: PubMed 30650121Prukop 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.
- Results publicationHajj 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
- Results publication: PubMed 27387831Attarian 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.
- Attarian et al., 2016Link provided by the sponsor.
- Chumakov et al., 2014Link provided by the sponsor.
- Mandel et al., 2015Link provided by the sponsor.
- Prukop et al., 2019Link provided by the sponsor.
- Attarian et al., Erratum, 2016Link provided by the sponsor.
- Hajj et al., 2019Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shahram Attarian, MD principal investigator
CHU La Timone, Marseille, France
Peter Young, MD principal investigator
University Hospital Munster, Germany
Teresa Sevilla, MD principal investigator
Hospital Universitari i Politécnic La Fe, Valencia, Spain
30 sites in 8 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing PXT3003 dose 1 and PXT3003 dose 2 in people with Charcot-Marie-Tooth Disease Type 1A, run by Pharnext S.C.A. at 30 sites in 8 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 30 sites in United States, France, Germany, Spain, United Kingdom and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Feb 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall Neuropathy Limitation Scale (ONLS) Total Score (time frame: From Baseline to Month 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02579759, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2020.