Charcot-Marie-Tooth DiseasePhase 2NCT01401257
Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
A Phase 2 study testing PXT3003 Low dose, PXT3003 Intermediate Dose and PXT3003 High Dose in people with Charcot-Marie-Tooth Disease and Hereditary Neuropathy With Liability to Pressure Palsies, run by Pharnext S.C.A. at 6 sites in France.
Trial summary
The present trial is a randomized, placebo-controlled study evaluating 3 different doses of PXT3003 in patients with CMT1A disease. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Charcot-Marie-Tooth Disease, Hereditary Neuropathy With Liability to Pressure Palsies, Genetic Disorders
- What is being tested?
- PXT3003 Low dose, PXT3003 Intermediate Dose and PXT3003 High Dose
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 6 sitesFrance
- Study dates
- Dec 2010to Dec 2012
- Phase
- Phase 2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- DNA proven CMT1A
- Muscle weakness in at least foot dorsiflexion (clinical assessment)
- Age between 18 and 65 years
- Male or non pregnant, non breastfeeding female
- CMT neuropathy score at screening ≤ 20
- Agrees to perform electrorophysiological studies and two cutaneous biopsies for determination of PMP22 expression and histology
- 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
- Patients with another neurological disease
- Patients using unauthorized concomitant treatments, ascorbic acid, opioids, levothyroxine and potentially neurotoxic drugs. Patients who can/agree to stop these medications 4 weeks before randomization can be included
- Patients who have participated in another trial of investigational drug within the past 30 days
- Concomitant major systemic disease
- Clinically significant history of unstable medical illness over the last 30 days (unstable angina…)
- History of significant hematologic, kidney, liver disease, or insulin-dependent diabetes
Show all 16Show fewer
- Clinically significant abnormalities on the prestudy laboratory evaluation, physical evaluation, electrocardiogram (ECG)
- ASAT/ALAT levels above the upper limit of normal (ULN). However, patients with an isolated elevation of either ASAT or ALAT (<1.5 ULN) can be included at investigators" discretion if the remaining liver function tests are normal and if ASAT or ALAT value is stable at 2 distinct evaluations in the month prior to inclusion
- Serum creatinine levels above the upper limit of normal
- Limited mental capacity or psychiatric disease rendering the subject unable to provide written informed consent or comply with evaluation procedures
- History of recent alcohol or drug abuse or non-adherence with treatment or other experimental protocols
- Female of childbearing potential (apart of patient using adequate contraceptive measures), pregnant or breast feeding
- Suspected inability to complete the study follow-up (foreign workers, transient visitors, tourists or any others for whom follow-up evaluation is not assured)
- Limb surgery in the six months before randomization or planned before completion of the trial
- Known hypersensitivity to any of the individual components of PXT3003
- Porphyria
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
France6 sites
Hôpital Roger Salengro
Lille, 59037
CHU Dupuytren
Limoges, 87042
CHU Lyon Sud
Lyon, 69495
Hôpital La Timone
Marseille, 13385
Hôtel Dieu
Nantes, 44093
Groupe Hospitalier Pitié-Salpétrière
Paris, 75013
About this study
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.
The present trial is a randomized, placebo-controlled study evaluating 3 different doses of PXT3003 in patients with CMT1A disease.
Read the detailed description
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.
- Conditions
- Charcot-Marie-Tooth Disease, Hereditary Neuropathy With Liability to Pressure Palsies, Genetic Disorders
- Being tested
- PXT3003 Low dose, PXT3003 Intermediate Dose, PXT3003 High Dose, Placebo
- Keywords
- PXT3003, Charcot-Marie-Tooth Disease, Hereditary Motor and Sensory Neuropathies
- Medical subject headings
- Charcot-Marie-Tooth Disease, Tomaculous neuropathy, Genetic Diseases, Inborn, Hereditary Sensory and Motor Neuropathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PXT3003 Low doseDrug
Also called Pleocompound PXT3003
Liquid,5 ml, twice a day, 12-month treatment
PXT3003 Intermediate DoseDrug
Also called Pleocompound PXT3003
Liquid,5 ml, twice a day, 12-month treatment
PXT3003 High DoseDrug
Also called Pleocompound PXT3003
Liquid,5 ml, twice a day, 12-month treatment
PlaceboOther
Also called Pleocompound PXT3003
Liquid,5 ml, twice a day, 12-month treatment
| Study group | Role | What they receive |
|---|---|---|
| PXT3003 Low dose | Experimental | Oral Liquid formulation, 1/100, bid, 12 months Receives: Drug: PXT3003 Low dose |
| PXT3003 Intermediate dose | Experimental | Oral Liquid formulation, 1/50, bid, 12 months Receives: Drug: PXT3003 Intermediate Dose |
| PXT3003 High dose | Experimental | Oral Liquid formulation, 1/10, bid, 12 months Receives: Drug: PXT3003 High Dose |
| Placebo | Placebo comparator | Oral Liquid formulation, bid, 12 months Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability of PXT3003
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.
Measured: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up
Secondary outcomes (5)
To Obtain Preliminary Data on the Efficacy of PXT3003 on Clinical Scores and Functional Tests
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.
Measured: Screening, randomization, 3-, 6-, 9- and 12-months treatment
To Assess the Pharmacodynamic Effect of PXT3003 on PMP22 mRNA Levels and Intra-epidermal Axon Density in Cutaneous Biopsy
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.
Measured: Randomization and 12-month treatment
To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters
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.
Measured: Screening, randomization, 3-, 6-, 9- and 12-month treatment
To Assess the Pharmacodynamic Effect of PXT3003 on a Series of Biochemical Biomarkers
Dosages of biochemical biomarkers in plasma.
Change from baseline after 3-month of treatment.
Measured: Randomization and 3-month treatment
To Assess the Plasma Concentrations of PXT3003
PXT3003 plasmatic concentrations after one administration (randomization) and after 1-,6-and 12-months of treatment.
Measured: Randomization, 1-, 6- and 12-month treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jul 2011 (estimated)
- Study startDec 2010
- Primary completionOct 2011
- Study completionDec 2012
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 (1)Papers the sponsor has linked to this study.
- Other trials for Charcot-Marie-Tooth DiseaseStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 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, Hôpital La TimoneViviane BERTRAND, PhD, Study director, Pharnext S.C.A.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01401257
- Sponsor's protocol ID
- CLN-PXT3003-01
- Status last verified
- Oct 2017
- First submitted
- 20 Jul 2011
- Last updated
- 22 Nov 2017
- 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 25519680
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01401257
- Acronym / sponsor ID
- CLN-PXT3003-01
- Conditions
- Charcot-Marie-Tooth Disease, Hereditary Neuropathy With Liability to Pressure Palsies, Genetic Disorders
- Keywords
- PXT3003, Charcot-Marie-Tooth Disease, Hereditary Motor and Sensory Neuropathies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Pharnext S.C.A.University, hospital or other
- Study start
- Dec 2010
- Primary completion
- Oct 2011 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 25 Jul 2011 (estimated)
- Results
- Posted 16 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present trial is a randomized, placebo-controlled study evaluating 3 different doses of PXT3003 in patients with CMT1A disease.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| PXT3003 Low dose | Experimental | Drug: PXT3003 Low doseOral Liquid formulation, 1/100, bid, 12 months |
| PXT3003 Intermediate dose | Experimental | Drug: PXT3003 Intermediate DoseOral Liquid formulation, 1/50, bid, 12 months |
| PXT3003 High dose | Experimental | Drug: PXT3003 High DoseOral Liquid formulation, 1/10, bid, 12 months |
| Placebo | Placebo comparator | Other: PlaceboOral Liquid formulation, bid, 12 months |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- DNA proven CMT1A
- Muscle weakness in at least foot dorsiflexion (clinical assessment)
- Age between 18 and 65 years
- Male or non pregnant, non breastfeeding female
- CMT neuropathy score at screening ≤ 20
Key exclusion criteria (16 listed)
- Patients with another neurological disease
- Patients using unauthorized concomitant treatments, ascorbic acid, opioids, levothyroxine and potentially neurotoxic drugs. Patients who can/agree to stop these medications 4 weeks before randomization can be included
- Patients who have participated in another trial of investigational drug within the past 30 days
- Concomitant major systemic disease
- Clinically significant history of unstable medical illness over the last 30 days (unstable angina…)
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 Low doseAlso: Pleocompound PXT3003Liquid,5 ml, twice a day, 12-month treatment | Drug | PXT3003 Low dose |
| PXT3003 Intermediate DoseAlso: Pleocompound PXT3003Liquid,5 ml, twice a day, 12-month treatment | Drug | PXT3003 Intermediate dose |
| PXT3003 High DoseAlso: Pleocompound PXT3003Liquid,5 ml, twice a day, 12-month treatment | Drug | PXT3003 High dose |
| PlaceboAlso: Pleocompound PXT3003Liquid,5 ml, twice a day, 12-month treatment | Other | Placebo |
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.
5 secondary outcomes
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
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
To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters
Time frame: Screening, randomization, 3-, 6-, 9- and 12-month treatment
To Assess the Pharmacodynamic Effect of PXT3003 on a Series of Biochemical Biomarkers
Time frame: Randomization and 3-month treatment
To Assess the Plasma Concentrations of PXT3003
Time frame: Randomization, 1-, 6- and 12-month treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: 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.
- Individual participant dataSharing planned: No
Related trials for Charcot-Marie-Tooth Disease
RecruitingObservational study
Studying Nerve Function and Structure in Charcot-Marie-Tooth Disease, Anti-MAG Neuropathy and CIDP
Charcot-Marie-Tooth, CMT1A
Recruiting
High-Tech Rehabilitation Pathway for Chronic Adult Neuromuscular Diseases - Fit4MedRob-Chronic MND Project
Amyotrophic Lateral Sclerosis, Chronic Inflammatory Demyelinating Neuropathy
Recruiting
Assessment of a Portable Digital Device for Quantified Analysis of Markerless Walking in Volunteers With Neuromuscular Diseases or Asymptomatic Volunteers
Spinal Muscular Atrophy (SMA), Charcot-Marie-Tooth
Not yet recruitingObservational study
Neurostructural and Biochemical Signatures of Tobacco Smoking in Mood Disorders
Major Depressive Disorder, Bipolar Disorder
Active, not recruiting
Tools for Therapeutic Evaluation in Charcot-Marie-Tooth Disease Type 1A: Outcome Measures and Biomarkers
Charcot-Marie-Tooth Disease Type 1A
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
Hôpital La Timone
Viviane BERTRAND, PhD study director
Pharnext S.C.A.
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PXT3003 Low dose, PXT3003 Intermediate Dose and PXT3003 High Dose in people with Charcot-Marie-Tooth Disease and Hereditary Neuropathy With Liability to Pressure Palsies, run by Pharnext S.C.A. at 6 sites in France.
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 7 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 22 Nov 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in France. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 16 Feb 2017). 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?
Safety and Tolerability of PXT3003 (time frame: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up). 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 NCT01401257, which also lists 1 linked publication.
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 22 Nov 2017; AzTrials last refreshed its copy on 6 Nov 2026.