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

NCT01401257 | Completed Phase 2 Results DMC

• 1 other identifier: CLN-PXT3003-01
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 6

Brief Summary

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

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

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  Randomization and 12-month treatment

• To Assess the Pharmacodynamic Effect of PXT3003 on Selected Neurophysiological Parameters

  Screening, randomization, 3-, 6-, 9- and 12-month treatment

• To Assess the Pharmacodynamic Effect of PXT3003 on a Series of Biochemical Biomarkers

  Randomization and 3-month treatment

• To Assess the Plasma Concentrations of PXT3003

  Randomization, 1-, 6- and 12-month treatment

Study Arms (4)

PXT3003 Low dose

EXPERIMENTAL

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

Drug: PXT3003 Low dose

PXT3003 Intermediate dose

EXPERIMENTAL

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

Drug: PXT3003 Intermediate Dose

PXT3003 High dose

EXPERIMENTAL

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

Drug: PXT3003 High Dose

Placebo

PLACEBO COMPARATOR

Oral Liquid formulation, bid, 12 months

Other: Placebo

Interventions

PXT3003 Low dose DRUG

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

Also known as: Pleocompound PXT3003

PXT3003 Low dose

PXT3003 Intermediate Dose DRUG

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

Also known as: Pleocompound PXT3003

PXT3003 Intermediate dose

PXT3003 High Dose DRUG

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

Also known as: Pleocompound PXT3003

PXT3003 High dose

Placebo OTHER

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

Also known as: Pleocompound PXT3003

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Pharnext S.C.A.: lead

Study Sites (6)

Hôpital Roger Salengro

Lille, 59037, France

Location

CHU Dupuytren

Limoges, 87042, France

Location

CHU Lyon Sud

Lyon, 69495, France

Location

Hôpital La Timone

Marseille, 13385, France

Location

Hôtel Dieu

Nantes, 44093, France

Location

Groupe Hospitalier Pitié-Salpétrière

Paris, 75013, France

Location

Related Publications (1)

• 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.

  PMID: 25519680 DERIVED

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease; Tomaculous neuropathy; Genetic Diseases, Inborn; Hereditary Sensory and Motor Neuropathy

Condition Hierarchy (Ancestors)

Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Pr Shahram ATTARIAN
• Organization: Hôpital La Timone, Marseille

shahram.attarian@ap-hm.fr

04 91 38 65

Study Officials

• Shahram ATTARIAN, MD

  Hôpital La Timone

  PRINCIPAL INVESTIGATOR

• Viviane BERTRAND, PhD

  Pharnext S.C.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 20, 2011
• First Posted: July 25, 2011
• Study Start: December 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: December 1, 2012
• Last Updated: November 22, 2017
• Results First Posted: February 16, 2017

Record last verified: 2017-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (6)