Investigating the safety of a drug to skip exon 51 (GSK2402968) in boys with Duchenne muscular dystrophy who are unable to walk
- Condition: Duchenne muscular dystrophy
- Start Date: July 2010
- Expected End Date: September 2011
- Status: Completed
- Location of trial: Europe, North America
What is the aim of the trial?
This phase 1 trial will test a drug (GSK2402968) that has been designed to skip exon 51 of the dystrophin gene. The investigators will be assessing the safety and tolerability of the drug in boys/adolescents who are unable to walk. Importantly they will also study the absorption and processing of the drug in their bodies.
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.
This drug has previously been tested in boys with Duchenne muscular dystrophy who are still able to walk and has generated some promising results. The main aim of this trial is to make sure there are no additional safety issues in wheelchair users. They will also measure how quickly the patch is absorbed, distributed and broken down by the body. Since these boys are less active than those tested previously who could still walk, the rate of absorption and breakdown of the patch could be different which may have implications for the dose required by them. This trial will provide essential information for future clinical trials in this patient group.
Who can be involved in the trial?
The trial is open to boys/adolescents with Duchenne muscular dystrophy over the age of 9 who have been using a wheelchair for at least 1 year but no more than 4 years. They must also have one of the mutations in the dystrophin gene that is correctable by GSK2402968.
Participants may be excluded if they have other health problems or if they are required to take certain medications.
For more information about how to get involved in trials please read our FAQ.
What happens during the trial?
The trial is a “dose escalation study” which means that they will test volunteers receiving the lowest dose first, and if this proves to be safe, the next dose level will be commenced, and so on up to the highest dose.
Participants will be assigned to one of a four groups. The first group have a single injection under the skin at a dose of 3 mg per kg of body weight. Participants in the other three groups will receive injections at 6 mg/kg, 9 mg/kg and 12 mg/kg. One quarter of the participants in each group will receive a placebo instead of GSK2402968. This is an inactive substance designed to resemble the drug being tested. Neither the clinicians nor the participants will know who is receiving the placebo.
Participants will have blood samples taken multiple times during the 24 hour period after their injection. They must return for follow-up visits at the study site which will include blood and urine tests and physical examinations three days, one week and four weeks after the injection.
Where is the study taking place?
The study will be taking place in:
• Ohio, USA
• France (location to be announced)
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?
This trial will assess how well tolerated and how safe GSK2402968 is in boys with Duchenne muscular dystrophy who are no longer able to walk. They will also be assessing the pharmacokinetics of the drug – that is how long the drug stays in the bloodstream and how the body gets rid of it. This may have implications for the dose required by them. At this stage, they are not assessing whether there is any improvement in muscle function because the participants in the trial will only be receiving a single injection of the drug which isn’t expected to be sufficient to improve muscle function.
This trial will provide essential information for future clinical trials in this patient group. If the drug is well tolerated, it is likely to be taken to a phase 2 trial where any possible benefits of the drug can be tested.
EU GSK Clinical Trials Call Center
Tel: +44 (0)208 990 4466
Who is funding this study?
Official name of the Trial:
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
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