Editorial note: This post refers to Pharnext and its experimental CMT1A therapy PXT3003. Pharnext is no longer operating, and PXT3003 is not an approved or available treatment. We have kept this post as part of our historical record.

The PREMIER Trial is being conducted in patients with mild-to-moderate CMT1A (the most common genetic subtype of Charcot-Marie-Tooth disease). It is expected to enroll approximately 350 participants, ages 16 to 65, with a confirmed genetic diagnosis of CMT1A. This international, multi-center, pivotal Phase III study planned to enroll patients at 50 sites worldwide (20 in the United States and 5 in Canada) and was set to begin by the end of March 2021.

The PREMIER Trial is a randomized, double-blind, two-arm, placebo-controlled study designed to confirm the safety and efficacy of PXT3003 in patients with CMT1A. Enrolled patients will be treated for 15 months.

As agreed with regulatory agencies, the primary efficacy endpoint is the Overall Neuropathy Limitation Score (ONLS) scale, which measures functional disability. Secondary endpoints include:

  1. 10-Meter Walk Test (10mWT)
  2. Quantified Muscular Testing (bilateral foot dorsiflexion dynamometry)
  3. Patient Global Impression of Severity (PGI-S)
  4. Patient Global Impression of Change (PGI-C)
  5. Charcot-Marie-Tooth Neuropathy Score, version 2 (CMTNS-v2)
  6. Quantified Muscular Testing (hand grip)

Safety and tolerability will be monitored throughout the study.

For those interested in participation, U.S. sites are listed and updated regularly at clinicaltrials.gov as they are activated and ready to screen and enroll patients. Sites in Canada, Europe, and Israel are also available on a dedicated patient web portal, which includes further information about the trial.

Pharnext is also continuing its ongoing Phase III Extension Study (CLN-PXT3003-03), an open-label study that enrolled 187 patients out of the 323 patients with mild-to-moderate CMT1A who participated in the first double-blind Phase III trial (PLEO-CMT). As of the time of this posting, 130 CMT1A patients were still being treated with high-dose PXT3003 and had been followed for more than two years to assess the safety, tolerability, and long-term efficacy of PXT3003. Pharnext planned to report top-line interim data from this extension study during Q2 2021.

You can also join HNF’s patient registry, GRIN, for clinical trial updates.