DMD, BMD: Phase 3 Trial Opens for Stop Codon Read-Through Drug

A large-scale, multinational phase 3 trial of the experimental drug ataluren has opened its first trial site, in Cincinnati, Ohio.

The trial is recruiting boys with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) caused by a nonsense mutation —  also known as a premature stop codon— in the dystrophin gene. This type of mutation causes cells to stop synthesizing a protein before the process is complete, resulting in a short, nonfunctional protein. Nonsense mutations are believed to cause DMD or BMD in approximately 10 to 15 percent of boys with these disorders.

Ataluren — sometimes referred to as a stop codon read-through drug — has the potential to overcome the effects of a nonsense mutation and allow functional dystrophin — the muscle protein that's missing in Duchenne MD and deficient in Becker MD — to be produced.

The orally delivered drug is being developed by PTC Therapeutics, a South Plainfield, N.J., biotechnology company, to which MDA gave a $1.5 million grant in 2005.

In 2010, PTC provided an analysis of results of a phase 2b trial of ataluren showing that a specific dosage regimen of the drug taken for 48 weeks slowed the decline of walking ability, as measured by the distance walked by trial participants in six minutes.

Trial to test ataluren's effect on walking

The new 48-week, phase 3 ataluren trial is slated to enroll 220 participants at multiple sites, with the goal of determining the effect of ataluren on walking ability in DMD or BMD caused by a nonsense mutation.

The only trial site currently open is at Cincinnati Children's Hospital Medical Center, but PTC plans to open sites around the world.

One group will take ataluren three times a day — 10 milligrams per kilogram of body weight in the morning and at midday and 20 milligrams per kilogram in the evening. Another group will take a placebo three times a day. Neither the trial participants nor the investigators will know who is taking which substance until after the trial has been completed.

Assessments will be performed every eight weeks.

The primary outcome measure is the six-minute walk test — the distance that can be walked in six minutes.

Secondary outcome measures include evaluations of physical function, assessments of activities of daily living and disease symptoms, quality-of-life measurements, safety tests, ataluren blood levels, and assessments of how well participants complied with the treatment.

Results are expected after June 2015.

To participate in the trial

Prospective participants in the phase 3 trial must:

  • be male;
  • be 7 to 16 years old;
  • have clinical evidence of dystrophin deficiency (DMD or BMD), with onset of symptoms by 6 years of age;
  • have a documented nonsense mutation in the dystrophin gene;
  • be able to walk at least 150 meters (492 feet) unassisted in six minutes, but be below the norm for their age on the distance walked in six minutes;
  • have been on a stable dosage of corticosteroids (prednisone, prednisolone or deflazacort) for at least six months prior to the start of the study; and
  • meet other criteria.

Participants must not:

  • have taken certain antibiotics (aminoglycoside type) within three months of the start of the study;
  • have started taking corticosteroids within six months of the start of the study;
  • have changed their corticosteroid regimen within three months of the start of the study;
  • have started or changed treatment for congestive heart failure within three months of the start of the study;
  • be taking certain anticoagulants ("blood thinners");
  • have undergone prior treatment with ataluren;
  • have been treated with immunosuppressive therapies other than corticosteroids;
  • expect to undergo a major surgical procedure within the one-year treatment period of the study;
  • require daytime ventilator assistance;
  • have uncontrolled symptoms and signs of congestive heart failure; or
  • have any prior or ongoing medical condition that, in the investigator's opinion, could adversely affect the participant's safety, make it unlikely that the participant would complete the trial, or could interfere with assessment of the study results.

To participate

Contact Diane Goetz at PTC Therapeutics at (908) 912-9256 or dgoetz@ptcbio.com; or call (866) 282-5873, or send an email to patientinfo@ptcbio.com. For the Cincinnati site, contact Paula Morehart at Cincinnati (Ohio) Children's Hospital Medical Center, at (513) 636-8967 or Paula.Morehart@cchmc.org.

Specific contact information for the other sites will be listed on ClinicalTrials.gov at Phase 3 Study of Ataluren in Patients with Nonsense Mutation Duchenne Muscular Dystrophy as it becomes available.

For more information

To learn more about PTC's plans for ataluren (formerly known as PTC124) in the United States and Europe, visit the PTC Therapeutics site and read DMD/BMD: Global Trial Planned of Experimental Drug Ataluren, in which PTC Therapeutics CEO Stuart Peltz discusses next steps for ataluren (Quest News Online, Feb. 21, 2013).

About Clinical Trials

About Clinical Trials

A clinical trial is a test, in humans, of an experimental treatment. Although it's possible that benefit may be derived from participating in a clinical trial, it's also possible that no benefit, or even harm, may occur.

MDA has no ability to influence who is chosen to participate in a clinical trial.

To learn more, see Learn About Clinical Studies and Being a Co-Adventurer, which is about neuromuscular disease clinical trials. To see a continuously updated database of clinical trials, go to ClinicalTrials.gov.

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