First US Exon-Skipping Trial Opens

Update (Nov. 5, 2012): Results announced in November 2012 showed the drug, now called drisapersen, reached blood levels approximately proportional to the injected dose at two of the three dosage levels tested and was not associated with serious adverse events. See Drisapersen Appears Safe in Non-Walking Boys With DMD.

Update (July 26, 2010):This story was updated with additional information provided by the Nationwide Children's Hospital study team.

A study of an experimental "exon-skipping" compound called GSK2402968 — designed to treat people with Duchenne muscular dystrophy (DMD) caused by any of a specific set of genetic mutations — is now open at Nationwide Children's Hospital in Columbus, Ohio. It's the first study of this type of drug to be conducted in the United States.

Funded by multinational pharmaceutical company GlaxoSmithKline, headquartered in the United Kingdom, the study will assess safety, tolerability and drug metabolism data in boys with DMD who are nonambulatory (unable to walk).

Kevin Flanigan will be the study’s principal investigator.

The drug, created by the Dutch biotechnology company Prosensa, in Leiden, the Netherlands, is designed to cause cells' protein-building machinery to skip over (ignore) faulty genetic instructions so that functional dystrophin, the protein missing in DMD, can be made from the remaining error-free instructions. Prosensa Vice President of Drug Discovery Judith van Deutekom received support from MDA to develop exon skipping when she was at Leiden University.

Trial participants will receive a subcutaneous (under the skin) injection of one of several doses of the treatment or placebo, followed by blood sample tests over the next 24 hours. They must return for follow-up visits to include blood and urine tests and physical examinations at the study site one week and four weeks after the injection.

"We're excited to see trials of exon skipping getting under way in the United States," said MDA Research & Medical Director Valerie Cwik. "This study also is among the first to test participants with DMD who are not walking, so we'll eagerly be awaiting results in this special group."

GlaxoSmithKline announced on Oct. 13, 2009, that it will develop and commercialize PRO051/ GSK2402968. (See Major Pharmaceutical Company Commits to Develop Exon-Skipping Drug.)

Trial enrollment is expected to begin next week. Researchers expect to enroll 32 participants.

Below is the trial description submitted by the Nationwide Children's study team, including participation criteria and contact information:

A double-blind, escalating dose, randomized, placebo-controlled study to assess the pharmacokinetics, safety and tolerability of single subcutaneous injections of GSK2402968 in non-ambulant subjects with Duchenne muscular dystrophy

Study Doctors

Kevin M. Flanigan, M.D.

Jerry R. Mendell, M.D.

Zarife Sahenk, M.D.

Chang-Yong Tsao, M.D.

Description: This study is directed to assess the pharmacokinetics, safety and tolerability of drug GSK2402968 in non-ambulant subjects with Duchenne muscular dystrophy. This drug is designed to induce skipping of exon 51 in the DMD gene.

The study will be conducted at Nationwide Children’s Hospital, in Columbus, Ohio.

To be considered to be part of the trial, subjects must:

  1. Be diagnosed with Duchenne muscular dystrophy.
  2. Have been in a wheelchair full time for at least one year, but no more than four years.  If a boy is walking, or uses a wheelchair only part time, he will not be a candidate for this study.
  3. Have one of the following out-of-frame deletions in the DMD gene:
  • exons 13-50
  • exons 29-50
  • exons 43-50
  • exons 45-50
  • exons 47-50
  • exons 48-50
  • exons 49-50
  • exon 50
  • exon 52

Subjects will undergo a screening that will include a DEXA scan and cardiology examination, along with blood tests.  More than two weeks later, they will receive a subcutaneous injection of the study agent, after which blood samples will be drawn over 24 hours. They will need to return to Nationwide Children’s Hospital for follow-up visits one week and four weeks after the injection for further blood and urine tests, and examination by a study doctor. 

Travel costs will be reimbursed under guidelines discussed with subjects before enrollment.

 If you are interested in this study, please contact the Study Coordinator:

 Xiomara Quintero Rosales, M.D.

(614) 722-6961


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