Phase 3 study of the effect of a drug to skip exon 51 (GSK2402968) on the muscle function of boys with Duchenne muscular dystrophy
- Condition: Duchenne muscular dystrophy
- Start Date: December 2010
- Expected End Date: December 2012
- Status: Ongoing but has finished recruiting patients
- Location of trial: Asia, Europe, North America, South America
What is the aim of the trial?
This phase 3 trial will test a drug (GSK2402968) that has been designed to skip exon 51 of the dystrophin gene. The investigators will be assessing the effect of GSK2402968 on the muscle function of boys with Duchenne muscular dystrophy and will continue to monitor the safety of the drug.
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. Previous trials however have not had enough participants treated for a sufficiently long time to determine if this production of dystrophin leads to an improvement in muscle function. This trial will primarily assess muscle function using the six minute walk test.
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 180 boys with Duchenne muscular dystrophy aged 5 years or older who are still able to walk at least 75 metres in six minutes. They must also have one of the mutations in the dystrophin gene that is correctable by GSK2402968. They must have been taking corticosteroids 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 either the treatment group or the placebo group. A placebo is an inactive substance designed to resemble the drug being tested. It is used to rule out any benefits a drug might exhibit because the recipients believe they are taking it. Neither the participants nor the clinicians will know who is receiving the placebo.
Both groups will receive a once weekly injection under the skin for 48 weeks. The main way to assess how the drug is affecting muscle function will be to measure the distance the participants can walk in six minutes. Other measures of muscle strength and breathing tests will also be done. Muscle biopsies to look for dystrophin protein will take place and periodically throughout the trial blood samples will be taken and general physical checks will be done. Changes in quality of life will be assessed by the completion of questionnaires.
Where is the study taking place?
The study will be taking place in up to 18 countries. The countries that have been announced so far are:
• France (Lille, Nantes, Paris, Toulouse)
• Germany (Freiburg, Muenchen, Goettingen, Essen, Kiel)
• Japan (Kumamoto, Saitama, Tokyo)
• South Korea (Seoul)
• Belgium (Leuven)
• Canada (Vancouver, London, Montreal)
• Chile (Santiago)
• Czech Republic (Brno and Praha)
• Italy (Roma, Milano, Messina)
• Netherlands (Leiden)
• Russia (Moscow)
• Poland (Warszawa)
• Spain (Madrid)
• Taiwan (Kaohsiung)
It is expected that sites in Canada and South America will also be announced in the near future and more countries will be added over time.
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 start to answer questions about whether GSK2402968 has a positive effect on the muscles of people with Duchenne who have mutations in the region of exon 51 of the dystrophin gene. If this trial is successful in proving that this treatment is effective and safe, GSK will then be in a position to apply to regulatory bodies for permission to market it and make it more widely available.
EU GSK Clinical Trials Call Center
Tel: +44 (0)208 990 4466
Who is funding this study?
Official name of the Trial:
A Clinical Study to Assess the Efficacy and Safety of GSK2402968 in Subjects With Duchenne Muscular Dystrophy (DMD114044)
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