Investigating two doses of a drug to skip exon 51 (GSK2402968) in boys with Duchenne muscular dystrophy
- Condition: Duchenne muscular dystrophy
- Start Date: September 2010
- Expected End Date: September 2012
- Status: Ongoing but has finished recruiting patients
- Location of trial: Australia, Europe, Middle East, United Kingdom
What is the aim of the trial?
This phase 2 trial will test two different doses of a drug (GSK2402968) that has been designed to skip exon 51 of the dystrophin gene. The study aims to find out if an intermittent treatment with GSK2402968 will lead to a better long-term safety profile, while maintaining effectiveness.
Duchenne muscular dystrophy is caused by a fault in the gene that carries the instructions for the essential muscle protein called dystrophin. Molecular patches (also known as 'antisense oligonucleotides') are short strands of DNA that can restore the production of dystrophin protein by a process called 'exon skipping'. Exon skipping works by masking the faulty part of the dystrophin gene, allowing a shortened but functional dystrophin protein to be produced, as is produced by people with the milder condition Becker muscular dystrophy.
GSK2402968 is designed to mask mutations in a region of the dystrophin gene called exon 51. Approximately 13% of Duchenne muscular dystrophy patients have a mutation in this region and could therefore potentially be treated with GSK2402968. To find out more information about exon skipping and how it works, please follow the link to our FAQ at the end of this page.
A phase 1/2 trial of GSK2402968 (previously known as PRO051) has already been completed and production of a shortened version of dystrophin protein was observed in muscle biopsies with no serious side effects. They received the drug once per week. A phase III trial of GSK2402968 is also currently being conducted by GSK as well as a trial in boys and young men who are unable to walk.
GSK have in-licensed GSK2402968 from Prosensa who led early clinical development. This means that GSK have a license to develop and market it. Exon skipping of exon 51 is also being trialled by the company AVI Biopharma using a chemical formulation of molecular patch that differs slightly from that used by Prosensa.
Who can be involved in the trial?
This trial aims to recruit 54 boys with Duchenne muscular dystrophy aged 5 years or older who are still able to walk at least 75 metres in six minutes and can rise from the floor relatively quickly. They must also have one of the mutations in the dystrophin gene that is correctable by GSK2402968. They must have been taking corticosteriods for at least 6 months and be on a stable dose. Some heart, liver and kidney problems, the use of certain medications and participation in some other clinical trials may make patients ineligible from the study.
For more information about how to get involved in trials please read our FAQ.
What happens during the trial?
Participants will be randomly assigned to 2 groups. The first will have a dose of drug injected under the skin every week for 48 weeks. The second group will have an intermittent schedule consisting of alternating weekly and twice weekly dosing for 6 weeks followed by a drug free period of 4 weeks for 48 weeks. One third of the boys in each group will receive placebo injections rather than the drug. A placebo is an inactive substance designed to resemble the drug being tested. Neither the patients nor the clinicians will know who is receiving the placebo.
The rate at which the molecular patch is absorbed, metabolised, and eliminated by the body will be measured to allow comparison of the two dosing schedules. The safety of the drug will be monitored by collecting blood and urine samples and general physical checks. Muscle function will be assessed by tests such as the distance the participants can walk in six minutes. Muscle biopsies will also be taken to look at the level of dystrophin protein.
Where is the study taking place?
The study will be taking place in:
• United Kingdom (London and Newcastle upon Tyne)
• Belgium (Gent)
• France (Paris)
• Germany (Freiburg and Essen)
• Turkey (Ankara)
• Australia (Westmead, NSW and Parkville, Vic)
• Netherlands (Nijmegen)
• Spain (Barcelona and Valencia)
For further information contact GSK using the details provided below.
In order for somebody to participate in the clinical trial, they need to be able to commit to travelling frequently to the team of people conducting the research, to allow close monitoring.
How could the results of the trial benefit patients?
The results from this trial will determine if it is safe and effective to give the exon skipping drug GSK2402968 intermittently rather than the once per week that has been tested in previous clinical trials. This information will help to inform doses to be tested in future clinical trials.
EU GSK Clinical Trials Call Center
Tel: +44 (0)208 990 4466
Who is funding this study?
Official name of the Trial:
Phase 2 Doubleblind Exploratory Study of GSK2402968 in Ambulant Subjects With Duchenne Muscular Dystrophy (DMD117)
Trial study number:
Further trial details:
For further information on the trial and detailed inclusion and exclusion please click on the link below. Sometimes these details can be quite technical. If you have any questions please discuss this with your clinician or contact the clinical trial organisers.
Link to terms in the glossary:
Background information and related links:
- More information about Duchenne muscular dystrophy
- Find out how exon skipping works
- News from the exon skipping trial
- Read about the exon 44 skipping trial