Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT)

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02579759
• Date of registration: 28/09/2015
• Prospective Registration: Yes
• Primary sponsor: Pharnext SA
• Public title: Phase III Trial Assessing the Efficacy and Safety of PXT3003 in CMT1A Patients (PLEO-CMT) PLEO-CMT
• Scientific title: International, Multi-center, Randomized, Double-blind, Placebo-controlled Phase III Study Assessing in Parallel Groups the Efficacy and Safety of 2 Doses of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A Treated 15 Months
• Date of first enrolment: December 2015
• Target sample size: 323
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02579759
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Belgium, Canada, France, Germany, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Peter Young, MD
• Affiliation: University Hospital Munster, Germany

• Name: Marianne De Visser, MD
• Affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

• Name: Florian Thomas, MD
• Affiliation: Saint-Louis University, Saint-Louis, USA

• Name: Shahram Attarian, MD
• Affiliation: CHU La Timone, Marseille, France

• Name: Teresa Sevilla, MD
• Affiliation: Hospital Universitari i Politécnic La Fe, Valencia, Spain

• Name: Jack Puymirat, MD
• Affiliation: University Hospital of Quebec

• Name: Philip Van Damme, MD
• Affiliation: UZ Leuven, Belgium

• Name: Mark Roberts, MD
• Affiliation: Salford Royal NHS Foundation Trust, Manchester, UK

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female, aged from 16 to 65 years;

- Patient with a proven genetic diagnosis of CMT1A;

- Mild-to-moderate severity assessed by Charcot-Marie-Tooth Neuropathy Score (version 2)
with a score >2 and =18;

- Muscle weakness in at least foot dorsiflexion;

- Motor nerve conduction of the ulnar nerve of at least 15 m/sec;

- 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:

- Any other associated cause of peripheral neuropathy such as diabetes;

- Patient with another significant neurological disease or a concomitant major systemic
disease;

- Clinically significant history of unstable medical illness since the last 30 days
(unstable angina, cancer…) that may jeopardize the participation in the study;

- Significant hematologic disease, hepatitis or liver failure, renal failure;

- Limb surgery within six months before randomization or planned before trial
completion;

- Clinically significant abnormalities on the pre-study laboratory evaluation, physical
evaluation, electrocardiogram (ECG);

- Elevated ASAT/ALAT (> 3 x ULN) and elevated serum creatinine levels (> 1.25 x ULN);

- History of recent alcohol or drug abuse or non-adherence with treatment or other
experimental protocols;

- Patient using unauthorized concomitant treatments including but not limited to
baclofen, naltrexone, sorbitol (pharmaceutical form), opioids, levothyroxin and
potentially neurotoxic drugs such as amiodarone, chloroquine, cancer drugs susceptible
to induce a peripheral neuropathy. Patient who can/agrees to stop these medications 4
weeks before randomization and during the whole study duration can be included;

- Female of childbearing potential (apart of patient using adequate contraceptive
measures), pregnant or breast feeding;

- Known hypersensitivity to any of the individual components of PXT3003;

- Porphyria as it is a contra indication to baclofen, and it may also induce neuropathy;

- Suspected inability to complete the study follow-up (foreign workers, transient
visitors, tourists or any others for whom follow-up evaluation is not assured);

- Limited mental capacity or psychiatric disease rendering the subject unable to provide
written informed consent or comply with evaluation procedures;

- Patient who has participated in another trial of investigational drug(s) within the
past 30 days;

- If a patient from the same family, living in the same household, has already been
included in this study, it will not be possible to include another patient from the
same family to avoid mixing of therapeutic units; therefore there would be a risk of
inversion of the blind treatments which could jeopardize the interpretation of study
results.



Age minimum: 16 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Charcot-Marie-Tooth Disease Type 1A

Intervention(s)

Drug: PXT3003 dose 1

Drug: placebo

Drug: PXT3003 dose 2

Primary Outcome(s)

Overall Neuropathy Limitation Scale (ONLS) Total Score [Time Frame: From Baseline to Month 15]

Secondary Outcome(s)

Mean of the CMTNS-v2 Sensory Score [Time Frame: From Baseline to Month 15]

Number of Subjects With at Least One TEAE [Time Frame: The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months)]

Incidence of SAEs [Time Frame: The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months).]

Incidence of AE Leading to Withdrawal of Study Drug [Time Frame: The period between the patient signing the informed consent and 30 days after the end of study (i.e. completion/early discontinuation/last contact as recorded on the 'Study Completion on Early Termination' form up to 15 months)]

Mean of the CMTNS-v2 Examination Score (CMTES-v2) [Time Frame: From Baseline to Month 15]

Mean of the Results at the Nine-Hole Peg Test (9-HPT) [Time Frame: From Baseline to Month 15]

Mean of Ten Meter Walking Test (10MWT) [Time Frame: From Baseline to Month 15]

Secondary ID(s)

CLN-PXT3003-02

2015-002378-19

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 27/02/2020
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02579759