Researchers are looking for people with Charcot-Marie-Tooth disease (CMT) to participate in a phase 2 clinical trial, sponsored by Acceleron Pharma, to test the investigational drug ACE-083 in people with CMT. The trial is the first to study ACE-083 in people with the disease.

Delivered by intramuscular injection, ACE-083 is based on a naturally occurring protein and is designed to enhance the body’s own promoters of muscle growth specifically in the muscles into which the drug is administered. Acceleron is developing the drug to treat diseases in which improving muscle atrophy and weakness may provide a clinical benefit. By targeting specific muscles such as the tibialis anterior (a long, narrow muscle on the front of the shin) in CMT, the company is aiming to improve ankle dorsiflexion. Ankle dorsiflexion can be weakened in CMT causing foot drop, and strengthening of these muscles has the potential to improve quality of life.

Goals of the trial include the assessment of safety and tolerability of ACE-083 in people with CMT1 and CMTX. In addition, researchers will evaluate efficacy, pharmacodynamics and pharmacokinetics. (Pharmacodynamics refers to the effects the drug has on the body, while pharmacokinetics refers to how the drug is absorbed, distributed and metabolized in the body.)

The trial will occur in two parts.

• In part 1, all participants will receive ACE-083. Investigators will assess the safety, tolerability and the optimal dose of ACE-083 in patients with CMT.
• Participants in Part 2 will be randomized to receive either ACE-083 or placebo. In this part of the trial, investigators aim to determine whether treatment with ACE-083 is associated with increased muscle volume, strength and function when compared to treatment with a placebo.

Total study duration for each patient will be approximately 24 weeks, including a 4-week screening period, a 12-week treatment period, and an 8-week follow-up period after the last dose. Participants will undergo testing including MRI, 6-minute walk test, 10-meter walk/run, gait parameters, Berg balance scale, muscle strength tested by handheld dynamometer, CMT Examination score version 2 (CMTES2) and CMT health index (CMT-HI).

To be eligible to participate, individuals must be at least 18 years old and have genetically confirmed CMT1 or CMTX, or have a first-degree relative with genetically confirmed CMT1 or CMTX and clinical signs/ symptoms of CMT1 or CMTX.

Eligible patients must also be experiencing mild to moderate weakness in their tibialis anterior muscles and meet additional criteria. Mild to moderate weakness of the tibialis anterior means the individual has some degree of foot drop, but is still able to lift their foot towards their shin against gravity. There may be weakness at the ankle (e.g., the individual may catch his or her toe when walking, or have to lift their foot high in order not to trip) but they still have some movement of the ankle.

Trial sites are located in Kansas, New Jersey and Pennsylvania, with additional sites expected to open soon in California, Florida, Iowa, Minnesota, New York and Utah. Travel expenses for participants will be covered for mileage, tolls, and parking. Depending on distance to the site, participants may also be covered for overnight hotel stays.

To learn more about this trial, go to clinicaltrials.gov and enter NCT03124459 into the search box, visit the trial website, or email clinicaltrials083@acceleronpharma.com.