An amendment in the protocol of two ongoing Phase 3 studies – the PLEO-CMT and PLEO-CMT-FU – testing the investigational drug PXT3003 in adults with Charcot-Marie-Tooth disease type 1A (CMT1A) was introduced to address stability issues with the drug’s highest dose arm, Pharnext announced.
In the PLEO-CMT study (NCT02579759), enrolled patients were randomly assigned to receive either a placebo (control) or one of two escalating doses of PXT3003 – dose 1 (5 ml) or dose 2 (5 ml), with dose 2 equal to twice the dose 1 – during a course of 15 months of treatment. The protocol established that all participants would undergo a nine-month extension study, called PLEO-CMT-FU (NCT03023540), in which all patients will receive PXT3003 treatment (either dose 1 or dose 2) to assess the long-term safety and tolerability of the drug. The follow-up study is currently recruiting participants.
After 12 months, however, stability became a concern in some batches of the high dose formulation (dose 2), but without any dangerous consequences for the patients taking it. To ensure, however, that patients receiving dose 2 are getting the full dose, Pharnext researchers decided to switch these patients to receive double the amount of dose 1 (2 X 5 mL) during the nine-month extension study. Patients in the placebo and dose 1 arm undergoing the PLEO-CMT study will continue the trial as planned, after which they’ll have the opportunity to participate in the PLEO-CMT-FU extension study for nine months.
“We have found a satisfactory solution for this unexpected stability event of the PXT3003 highest dose that was not previously investigated in our Phase 2 trial,” Daniel Cohen, MD and PhD, co-founder and CEO of Pharnext, said in a press release. “All our objectives and development milestones remain unchanged and we look forward to bringing this innovative therapy to CMT1A patients.”
The PLEO-CMT study’s final data collection date for primary outcome measures is expected by March 2018, which will be the basis for a market approval submission in the first quarter of 2019. Data from the follow-up study regarding PXT3003’s long-term safety will then be available to regulatory authorities during their revision of the marketing authorization application. Pharnext hopes to receive marketing approval for PXT3003 in the second half of 2019.
An independent safety review board previously reviewed safety data from a Phase 2 trial with PXT3003, and recommended the continuation to Phase 3, as no safety concerns for either PXT3003 doses were found.