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

NCT ID: NCT01401257

Last Updated: 2017-11-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2012-12-31

Brief Summary

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.

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

PXT3003 Low dose

Oral Liquid formulation, 1/100, bid, 12 months

Group Type: EXPERIMENTAL

PXT3003 Low dose

Intervention Type: DRUG

Liquid,5 ml, twice a day, 12-month treatment

PXT3003 Intermediate dose

Oral Liquid formulation, 1/50, bid, 12 months

Group Type: EXPERIMENTAL

PXT3003 Intermediate Dose

Intervention Type: DRUG

Liquid,5 ml, twice a day, 12-month treatment

PXT3003 High dose

Oral Liquid formulation, 1/10, bid, 12 months

Group Type: EXPERIMENTAL

PXT3003 High Dose

Intervention Type: DRUG

Liquid,5 ml, twice a day, 12-month treatment

Placebo

Oral Liquid formulation, bid, 12 months

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Liquid,5 ml, twice a day, 12-month treatment

Interventions

PXT3003 Low dose

Liquid,5 ml, twice a day, 12-month treatment

Intervention Type: DRUG

PXT3003 Intermediate Dose

Liquid,5 ml, twice a day, 12-month treatment

Intervention Type: DRUG

PXT3003 High Dose

Liquid,5 ml, twice a day, 12-month treatment

Intervention Type: DRUG

Placebo

Liquid,5 ml, twice a day, 12-month treatment

Intervention Type: OTHER

Other Intervention Names

Pleocompound PXT3003; Pleocompound PXT3003; Pleocompound PXT3003; Pleocompound PXT3003

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharnext S.C.A.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shahram ATTARIAN, MD

Role: PRINCIPAL_INVESTIGATOR

Hôpital La Timone

Viviane BERTRAND, PhD

Role: STUDY_DIRECTOR

Pharnext S.C.A.

Locations

Hôpital Roger Salengro

Lille, , France

CHU Dupuytren

Limoges, , France

CHU Lyon Sud

Lyon, , France

Hôpital La Timone

Marseille, , France

Hôtel Dieu

Nantes, , France

Groupe Hospitalier Pitié-Salpétrière

Paris, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 25519680 (View on PubMed)

Other Identifiers

CLN-PXT3003-01

Identifier Type: -

Identifier Source: org_study_id