- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01401257
Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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-
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Lille, France, 59037
- Hôpital Roger Salengro
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Limoges, France, 87042
- Chu Dupuytren
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Lyon, France, 69495
- CHU Lyon Sud
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Marseille, France, 13385
- Hôpital La Timone
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Nantes, France, 44093
- Hotel Dieu
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Paris, France, 75013
- Groupe Hospitalier Pitie-Salpetriere
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: PXT3003 Low dose
Oral Liquid formulation, 1/100, bid, 12 months
|
Liquid,5 ml, twice a day, 12-month treatment
Other Names:
|
Experimental: PXT3003 Intermediate dose
Oral Liquid formulation, 1/50, bid, 12 months
|
Liquid,5 ml, twice a day, 12-month treatment
Other Names:
|
Experimental: PXT3003 High dose
Oral Liquid formulation, 1/10, bid, 12 months
|
Liquid,5 ml, twice a day, 12-month treatment
Other Names:
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Placebo Comparator: Placebo
Oral Liquid formulation, bid, 12 months
|
Liquid,5 ml, twice a day, 12-month treatment
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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. |
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
|
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. |
Randomization and 12-month treatment
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To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters
Time Frame: Screening, randomization, 3-, 6-, 9- and 12-month treatment
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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. |
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
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Dosages of biochemical biomarkers in plasma. Change from baseline after 3-month of treatment. |
Randomization and 3-month treatment
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To Assess the Plasma Concentrations of PXT3003
Time Frame: Randomization, 1-, 6- and 12-month treatment
|
PXT3003 plasmatic concentrations after one administration (randomization) and after 1-,6-and 12-months of treatment.
|
Randomization, 1-, 6- and 12-month treatment
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Shahram ATTARIAN, MD, Hôpital La Timone
- Study Director: Viviane BERTRAND, PhD, Pharnext SA
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Congenital Abnormalities
- Neuromuscular Diseases
- Stomatognathic Diseases
- Neurodegenerative Diseases
- Peripheral Nervous System Diseases
- Heredodegenerative Disorders, Nervous System
- Nervous System Malformations
- Polyneuropathies
- Genetic Diseases, Inborn
- Tooth Diseases
- Nerve Compression Syndromes
- Charcot-Marie-Tooth Disease
- Hereditary Sensory and Motor Neuropathy
Other Study ID Numbers
- CLN-PXT3003-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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