Assessing Long Term Safety and Tolerability of PXT3003 in Patients With Charcot-Marie-Tooth Disease Type 1A

PXT3003 is a rational design, fixed combination of low-dose (RS) baclofen, naltrexone
hydrochloride and D-sorbitol. The use of PXT3003 in a multicenter, randomised, placebo
controlled phase II study (CLN-PXT3003-01) was well-tolerated and safe in patients with CMT1A
for the three dose-levels investigated (Attarian et al., 2014). The intermediate and high
dose of PXT3003 demonstrated an improvement of disability in this patient population.

Subsequently a multicenter, randomised, placebo controlled phase III study (CLN-PXT3003-02)
to assess the efficacy and safety of PXT3003 in the treatment of patients with CMT1A was
initiated in December 2015. In March 2017 the first patients will have completed the 15-month
treatment with PXT3003. September 18th 2017, the PXT3003 dose 2 was prematurely discontinued
by the Sponsor. Thereafter, patients will be allowed for entry in this extension study
(CLN-PXT3003-03) for a 9-month treatment with PXT3003. Thus patients initially randomised to
active treatment will have used PXT3003 for up to 24 months, whereas patients initially
randomized to inactive treatment will have used PXT3003 for up to 9 months.

Inclusion Criteria after September 18th 2017:

- Patients previously randomized to study CLN-PXT3003-02 under placebo and dose 1 and
having completed 15 months of double-blind treatment in that study, including all
procedures required at the Study Termination visit (V6) or

- Patients previously randomized to the initial study CLN-PXT3003-02 under dose 2,
prematurely discontinued following sponsor decision, and having performed all
procedures required at the Study Termination visit (V6)

- Patients whose V6 was performed within 4 weeks before entering the extension study or
if not done must have a new baseline visit (VB)

- Female patients must agree to continue using an approved method of birth control
throughout the extension study

- Patients must sign a written informed consent, specific to the extension study, in
order to participate in this study. In case of minor children aged 16 to 18 years,
both parent' and children's consents should be collected

Inclusion Criteria until September 18th 2017:

- Patients must have completed 15 months of double-blind treatment in the primary study
CLN-PXT3003-02, including all procedures required at the Study Termination visit (V6)

- Female patients must agree to continue using an approved method of birth control
throughout the extension study

- Patients must sign a written informed consent, specific to the extension study, in
order to participate in this study. In case of minor children aged 16 to 18 years,
both parent' and children's consents should be collected

Exclusion Criteria:

- Any clinically significant change in health status that, in the opinion of the
Investigator, would prevent the subject from participating in this study or
successfully completing this study

- Any unauthorized concomitant treatments, as study CLN-PXT3003-02 (e.g. 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 peripheral neuropathy)