Phase 3 Trial of Potential Treatment for CMT Type 1A, PXT3003, Cleared to Continue by Independent Board

Intermediate analyses were positive for a Phase 3 clinical trial evaluating Pharnext’s PXT3003 as a possible treatment for people with Charcot-Marie-Tooth disease type 1A (CMT1A).

Results of the two planned analyses — conducted by Philippe Lehert, a member of the study’s Independent Data Safety Monitoring Board — confirmed the trial’s design and that data being collected were of a high enough quality to allow an accurate evaluation of PXT3003’s safety and efficacy. The board particularly looked at the trial’s primary goal of measuring changes in disability using Overall Neuropathy Limitation Scale (ONLS) scores. No changes to the trial plan were requested, the company said in a press release.

The ongoing pivotal study, called PLEO-CMT (NCT02579759), is testing PXT3003 in 323 patients with mild-to-moderate CMT1A at 30 clinical sites in Europe, the U.S., and Canada. Patients are randomly assigned to receive one of two escalating doses of PXT3003 as a liquid solution, or placebo, twice daily for up to 15 months. Both treatment doses are 5 ml of solution, but the concentration differs.

Some problems with the stability of the therapy at the higher concentration were detected in the trial in September, raising concerns about the dose’s accuracy. These issues were resolved with no additional risk for the patients, and did not affect the trial’s progression.

Two previous intermediate safety analyses also confirmed the treatment was safe, with no serious adverse events being reported that required a change in trial design or its progression.

“These two analyses are additional steps successfully reached for the PLEO-CMT study,” Daniel Cohen, co-founder and CEO of Pharnext, said in the release. “They allow us to confirm the schedule for final results by the second half of 2018.”

PXT3003 is a fixed low-dose combination of baclofen (brand name, Lioresal), a muscle relaxer; naltrexone, an opioid antagonist; and sorbitol, a laxative. This combination has been shown to trigger molecular mechanisms that help manage symptoms of CMT1A. In particular, this treatment is thought to reduce levels of PMP22 protein, a faulty protein found in high amounts in CMT patients that causes nerve damage.

Data from an earlier Phase 2 (NCT01401257) clinical trial in 80 adults with CMT1A showed that higher doses of PXT3003 significantly improved disability scores compared to placebo. The treatment was found to be safe overall and well-tolerated, with no differences in the frequency of adverse events between placebo and PXT3003-treated groups.

The Phase 3 trial will measure treatment effectiveness by comparing ONLS scores at 12 and 15 months of treatment against baseline, or scores registered at the study’s start. It is expected to conclude in March 2018.

Trial participants will be invited to continue treatment in a nine-month extension study, called PLEO-CMT-FU (NCT03023540), which will test the long-term safety and tolerability of the drug. Treated patients in the PLEO-CMT study will continue on their assigned dose, while placebo patients will be randomly given PXT3003 at either of the two doses.

PXT3003 was named an orphan drug by the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) as a potential CMT1A treatment in 2014.