Phase II, Randomized, Placebo-controlled Trial in Patients With Charcot-marie-tooth Disease Type 1A - Full Text View

Purpose

The present trial is a randomized, placebo-controlled study evaluating 3 different doses of PXT3003 in patients with CMT1A disease.

Condition	Intervention	Phase
Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsies Genetic Disorders Tooth Disorders	Drug: PXT3003 Other: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
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.

Resource links provided by NLM:

Genetics Home Reference related topics: Charcot-Marie-Tooth disease hereditary neuropathy with liability to pressure palsies

MedlinePlus related topics: Charcot-Marie-Tooth Disease Tooth Disorders

Genetic and Rare Diseases Information Center resources: Charcot-Marie-Tooth Disease Hereditary Neuropathy With Liability to Pressure Palsy Roussy Levy Syndrome Charcot-Marie-Tooth Disease Type 1A Charcot-Marie-Tooth Disease Type 1

U.S. FDA Resources

Further study details as provided by Pharnext SA:

Primary Outcome Measures:

Safety and tolerability of PXT3003 [ Time Frame: Screening, randomization, 1-, 3-, 6-, 9-, 12-month treatment and 1-month follow-up ] [ Designated as safety issue: Yes ]
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.

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]
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.
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 ] [ Designated as safety issue: No ]
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.
To assess the pharmacodynamic effect of PXT3003 on selected neurophysiological parameters [ Time Frame: Screening, randomization, 3-, 6-, 9- and 12-month treatment ] [ Designated as safety issue: No ]
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.
To assess the pharmacodynamic effect of PXT3003 on a series of biochemical biomarkers [ Time Frame: Randomization and 3-month treatment ] [ Designated as safety issue: No ]
Dosages of biochemical biomarkers in plasma.

Change from baseline after 3-month of treatment.
To assess the plasma concentrations of PXT3003 [ Time Frame: Randomization, 1-, 6- and 12-month treatment ] [ Designated as safety issue: Yes ]
PXT3003 plasmatic concentrations after one administration (randomization) and after 1-,6-and 12-months of treatment.


Enrollment:	80
Study Start Date:	December 2010
Study Completion Date:	December 2012
Primary Completion Date:	October 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: PXT3003 Low dose Oral Liquid formulation, 1/100, bid, 12 months	Drug: PXT3003 Liquid,5 ml, twice a day, 12-month treatment Other Name: Pleocompound PXT3003
Experimental: PXT3003 Intermediate dose Oral Liquid formulation, 1/50, bid, 12 months	Drug: PXT3003 Liquid,5 ml, twice a day, 12-month treatment Other Name: Pleocompound PXT3003
Experimental: PXT3003 High dose Oral Liquid formulation, 1/10, bid, 12 months	Drug: PXT3003 Liquid,5 ml, twice a day, 12-month treatment Other Name: Pleocompound PXT3003
Placebo Comparator: Placebo Oral Liquid formulation, bid, 12 months	Other: Placebo Liquid,5 ml, twice a day, 12-month treatment Other Name: Pleocompound PXT3003

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.

Eligibility


Ages Eligible for Study:	18 Years to 65 Years (Adult)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01401257

Locations


France
Hôpital Roger Salengro
Lille, France, 59037
CHU Dupuytren
Limoges, France, 87042
CHU Lyon Sud
Lyon, France, 69495
Hôpital La Timone
Marseille, France, 13385
Hôtel Dieu
Nantes, France, 44093
Groupe Hospitalier Pitié-Salpétrière
Paris, France, 75013

Sponsors and Collaborators

Pharnext SA

Investigators


Principal Investigator:	Shahram ATTARIAN, MD	Hôpital La Timone
Study Director:	Viviane BERTRAND, PhD	Pharnext SA

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Attarian S, Vallat JM, Magy L, Funalot B, Gonnaud PM, Lacour A, Péréon 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-Grès 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.


Responsible Party:	Pharnext SA
ClinicalTrials.gov Identifier:	NCT01401257 History of Changes
Other Study ID Numbers:	CLN-PXT3003-01
Study First Received:	July 20, 2011
Last Updated:	September 11, 2013
Health Authority:	France: Conseil National de l'Ordre des Médecins

Keywords provided by Pharnext SA:


PXT3003 Charcot-Marie-Tooth Disease Hereditary Motor and Sensory Neuropathies

Additional relevant MeSH terms:


Disease Tooth Diseases Charcot-Marie-Tooth Disease Nerve Compression Syndromes Hereditary Sensory and Motor Neuropathy Pathologic Processes Stomatognathic Diseases Nervous System Malformations	Nervous System Diseases Heredodegenerative Disorders, Nervous System Neurodegenerative Diseases Polyneuropathies Peripheral Nervous System Diseases Neuromuscular Diseases Congenital Abnormalities Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on September 30, 2016