Pharnext, an advanced clinical stage biopharmaceutical company, announced the opening of the first US trial site for its PLEO-CMT pivotal phase 3 clinical trial of its lead pleodrug PXT3003 in Charcot-Marie-Tooth disease type 1A (CMT1A). The clinical trial, which began enrolling patients in December 2015 in Europe, is intended to determine whether PXT3003 is effective and well tolerated in patients with CMT1A. PXT3003, developed using Pharnext's Pleotherapy R&D platform, is an oral fixed-low dose combination of (RS)-baclofen, naltrexone hydrochloride and D-sorbitol.

The study expects to enroll a total of 300 patients across 28 centres in the United States (California, Connecticut, Florida, Massachusetts, Minnesota, Missouri, New York and Washington) and in Europe (France, Germany, UK, Spain, the Netherlands and Belgium). These centres will be progressively opened and activated in 2016. The first trial site in the US that has just been activated is located in the Saint-Louis University (Missouri).

The exploratory phase 2 trial of PXT3003 demonstrated safety, tolerability and improvements beyond stabilization of CMT1A patient disability as published in the Orphanet Journal of Rare Diseases.

Daniel Cohen, M.D., Ph.D., chairman, chief executive officer and co-founder of Pharnext, said, "Opening the first US trial site is an important milestone in our PLEO-CMT phase 3 trial programme after opening the first sites in France, Germany and Belgium since December 2015. Our hope is that this international phase 3 study will support the promising results we saw in previous studies with PXT3003 and bring long-needed relief to patients suffering from CMT1A."

Allison Moore, founder and chief executive officer of the Hereditary Neuropathy Foundation (HNF), said, "There is currently no approved treatment for patients suffering with CMT. We are strong supporters of Pharnext's initiative to bring help to these patients in the form of an effective therapy. We are happy to be able to provide information about this clinical trial on our website and provide patients with the information they need to find trial sites. We have been supported by Pharnext since 2014 to improve awareness of CMT and other rare neuropathies notably with such resources as the Global Registry for Inherited Neuropathies (GRIN) or the CMT Connect programme launched recently in the US."

Charcot-Marie-Tooth (CMT) disease encompasses a heterogeneous group of inherited, progressive, chronic peripheral neuropathies. CMT type 1A (CMT1A), the most common type of CMT, is an orphan disease affecting at least 125,000 people in Europe and the US. The genetic mutation responsible for CMT1A is a duplication of the PMP 22 gene coding for a peripheral myelin protein. Overexpression of this gene causes degradation of the neuronal sheath (myelin) responsible for nerve dysfunction, followed by loss of nerve conduction. As a result of peripheral nerve degradation, patients suffer from progressive muscle atrophy of legs and arms causing walking, running, balance problems and abnormal hand functioning. CMT1A patients end up in wheelchairs in at least 5 per cent of cases. They might also suffer from mild to moderate sensitive disorders. First symptoms usually appear during adolescence and will progressively evolve through patients' life.

To date, no curative or symptomatic medications have been approved and treatment consists of supportive care such as orthotics, leg braces, physical and occupational therapy or surgery.

PLEO-CMT is a pivotal, multi-center, randomized, double blind, placebo-controlled, three-arm phase 3 study which will enroll patients aged 16 and older with mild to moderate CMT1A. Diagnosis of CMT1A will be confirmed genetically through detection of PMP22 gene duplication. Over 15 months, Pharnext will compare in parallel groups the efficacy and safety of two orally administered dosage variations of PXT3003 to placebo. Efficacy will be assessed through one primary endpoint: change in the ONLS score at 12 and 15 months of treatment to measure improvement of patients' disability with PXT3003. Additional secondary outcome measures will be assessed including functional and electrophysiological endpoints. A nine month follow-up study is planned thereafter, where all patients who will have completed the first 15 months, will receive the active PXT3003 dose.