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

PXT3003, is a fixed dose combination of (RS)-baclofen, naltrexone hydrochloride and
D-sorbitol selected via a Systems Biology approach and developed by Pharnext, with the aim to
lower toxic PMP22 gene over-expression in CMT1A. On September 18th 2017, the PXT3003 dose 2
was prematurely discontinued, due to an unexpected investigational medicinal product quality
event (failed month 18 stability testing). The independent data safety monitoring committee
did not identify any safety concern on September 5th 2017. All patients randomised to dose 2
were requested to undergo the end of study visit, and were offered to enter the extension
study (CLN-PXT3003-03).

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.