assessing long term safety and tolerability of pxt3003 in patients with charcot-marie-tooth disease type 1a

Conditions: Charcot-Marie-Tooth Disease, Type IA

Summary: all randomised patients with charcot-marie-tooth type 1a (cmt1a) who completed the primary study cln-pxt3003-02, i.e. treatment with pxt3003 or placebo, are eligible to continue in the extension study cln-pxt3003-03. period 1: patients randomised to pxt3003 dose 1 or placebo in the primary study (cln-pxt3003-02) continued in the extension study on pxt3003 dose 1 (5 ml). patients randomised to pxt3003 dose 2 (5 ml) in the primary study (cln-pxt3003-02) continued in the extension study on pxt3003 dose 2 or pxt3003 twice dose 1 (2x5 ml). period 2: all patients continue on twice dose 1 (2x5ml).

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 completed the 15-month treatment with pxt3003 and rolled over into the extension study cln-pxt3003-03. during period 1 (9 months), patients that were randomised to pxt3003 dose 1 or placebo in the primary study (cln-pxt3003-02) continued in the extension study on pxt3003 dose 1 (5 ml). patients randomised to pxt3003 dose 2 (5 ml) in the primary study (cln-pxt3003-02) continued in the extension study on on pxt3003 dose 2 or pxt3003 twice dose 1 (2x5 ml). during period 2, all patients continue on twice dose 1 (2x5ml).

Eligibility criteria:
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)

Keywords: charcot marie tooth type 1a peripheral neuropathy pxt3003