Investigating the skipping of exon 44 as a treatment for Duchenne muscular dystrophy
- Condition: Duchenne muscular dystrophy
- Start Date: December 2009
- Expected End Date: December 2011
- Status: Ongoing but is not recruiting patients
- Location of trial: Europe
What is the aim of the trial?
This Phase 1/2 trial is looking at whether the experimental drug PRO044 is safe and effective as a therapy for people with Duchenne muscular dystrophy with a mutation in a specific region of the dystrophin gene called exon 44.
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.
Since the the genetic errors causing Duchenne occur in different places along the very large dystrophin gene, many different molecular patches will need to be specially tailor made to treat the 83% of patients who in theory could be treated with exon skipping.
PRO044 is designed to mask mutations in a region of the dystrophin gene called exon 44. Approximately 6% of Duchenne muscular dystrophy patients have a mutation in this region and could therefore be treatable with PRO044. 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.
The Dutch pharmaceutical company Prosensa Therapeutics is conducting this study. They have already completed a phase 1/2 trial of GSK2402968 (previously known as PRO051). This molecular patch is designed to skip exon 51 and is applicable to approximately 13% of Duchenne muscular dystrophy patients. Testing of this patch is continuing in phase 2 and 3 clinical trials conducted by Prosensa’s strategic partner GSK who has in-licensed GSK2402968. This means that GSK have a license to develop and market it. GSK2402968. Exon skipping is also being trialed in the UK using a chemical formulation of molecular patch that differs slightly from that used by Prosensa.
Who can be involved in the trial?
This trial of PRO044 has recruited 12 boys aged between five and 16 years with a diagnosis of Duchenne muscular dystrophy caused by a mutation in the region of exon 44 of the dystrophin gene.
Boys were excluded from participating in the trial if they had participated in another trial within the last six months, were using certain medication or had another illness.
Please note that all patients for this study have already been identified and lined up in the participating trial centres.
For more details of who was eligible to participate in the trial, see ‘Further trial details’ below.
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, they will give it to those receiving the next dose, and so on up to the highest dose.
Participants will be assigned to one of a maximum of four sequential groups. The first group will be administered 0.5 mg/kg of PRO044 by injection under the skin once a week for five weeks. Participants in the other three groups will receive injections of PRO044 at the same intervals, but at 1.5 mg/kg, 5 mg/kg and 8 mg/kg.
Dystrophin production will be analysed in muscle biopsies within 13 weeks of treatment with PRO044. Participants will also be monitored to determine the safety of treatment with PRO044 and how it is metabolised by the body.
Where is the study taking place?
This trial is being carried out in four locations:
- Leuven, Belgium
- Gothenburg, Sweden
- Ferrara, Italy
- Leiden, the Netherlands
In most circumstances, for somebody to participate in a clinical trial, they need to live near the team of people who are conducting the research, because they need to be closely monitored.
How could the results of the trial benefit patients?
The results from this trial may indicate that treatment with PRO044 benefits people with Duchenne with mutations in the region of exon 44 of the dystrophin gene. If so, PRO044 may enter a Phase 2 and 3 trials in larger study groups, taking it a step closer to clinical use in people with this condition.
Dr Nathalie Goemans
UZ Leuven, Leuven, Belgium, 3000
Tel: +32 (0)16 343845
Who is funding this study?
Official name of the Trial:
A Phase 1/2a, open label, escalating dose, pilot study to assess the effect, safety, tolerability and pharmacokinetics of multiple subcutaneous doses of PRO044 in patients 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.