Patient Enrollment Complete for PREMIER Trial of PXT3003

Vanda Pinto, PhD avatar

by Vanda Pinto, PhD |

Share this article:

Share article via email
PXT3003 | Charcot-Marie-Tooth News | CMT1A | clinical trial illustration

Enrollment into Pharnext’s pivotal Phase 3 PREMIER clinical trial, testing the effectiveness and safety of PXT3003 for people with mild-to-moderate Charcot-Marie-Tooth type 1A (CMT1A), is complete.

The study exceeded its target number of participants, recruiting 387 patients in 52 centers across the U.S., Canada, Europe, and Israel. Top-line data are expected in the last quarter of 2023.

“Completing enrollment of the Pivotal Phase III study of PXT3003, the PREMIER trial, represents a significant milestone for Pharnext and we are delighted that the study has completed enrollment on schedule across an international range of trial centers,” David Horn Solomon, PhD, Pharnext’s CEO, said in a press release. “It brings us one step closer to a potential treatment for those with CMT1A, a debilitating disease which affects around 1.5 million people globally.”

PXT3003 is an oral medication made up of baclofen, naltrexone, and D-sorbitol. All three compounds work by reducing PMP22 protein levels in different ways, leading to improvements in neuromuscular function.

Recommended Reading
stem cells | Charcot-Marie-Tooth News | illustration of nerve cell and axons

Stem Cells May Boost Myelin Production in CMT1A, Study Suggests

The therapy’s safety and effectiveness at different doses originally was tested in the Phase 3 PLEO-CMT clinical trial (NCT02579759) in people with mild-to-moderate CMT1A. Participants received either a high dose or a low dose of PXT3003, or a placebo, twice a day for 15 months.

Data from this study showed the high PXT3003 dose could ease disabilities, assessed using the overall neuropathy limitations scale (ONLS), which evaluates limitations in upper and lower limbs for everyday activities. The treatment also was found to be safe and well-tolerated.

However, stability issues causing crystals to form inside bottles with the high dose led to all patients in Germany discontinuing the study, as required by the local regulatory authorities, and all patients receiving the high dose were taken off the medication.

Next, an open-label extension study, called PLEO-CMT-FU (NCT03023540), was opened for participants who completed PLEO-CMT. This trial was divided into two periods. In the first period, lasting nine months, patients continued to receive the same dose of PXT3003 as in the original trial, although the high dose was given at twice the volume of the low dose formulation. Participants previously on a placebo began receiving the low dose of PXT3003. In the second period, all patients were switched to the high dose of PXT3003.

According to the company, PXT3003’s safety and tolerability are evaluated every three months and changes in ONLS every six months. This ongoing trial, which has continued to show positive results, is expected to end in December 2024. Findings will be released once a year.

The PREMIER trial (NCT04762758) was requested by regulatory agencies in the U.S. and Europe due to the formulation problems in the PLEO-CMT study. Participants with mild-to-moderate CMT1A ages 16 to 65 will be assigned randomly to receive either oral PXT3003 twice a day (the high dose) or a placebo, for 15 months.

Researchers plan to evaluate changes in ONLS, as well as in other outcome measures, such as the 10-meter walk test — an evaluation of walking speed — and patient global impression scales, which measure several aspects of a patient’s health and clinical status. Disease severity, assessed using the CMT Neuropathy Score and changes in hand grip, also will be determined.

Safety and tolerability will be monitored throughout the trial.

“We are grateful to the patients and investigators participating in this trial. If approved, PXT3003 has the potential to help transform the lives of those who live with CMT1A,” said Burkhard Blank, MD, chief medical officer at Pharnext.