Institute of Child Health

This trial, funded by the department of Health was completed in 2009 and has been published in the journal Lancet Neurology (Vol.8.issue 10,pages 918-928,October 2009).

The scope of this phase I/II study was to assess efficacy as a proof of principle (dystrophin production) and safety of intramuscular administered morpholino oligomer directed against exon 51 (AVI-4658 PMO). 

For more information visit

• http://www.clinicaltrials.gov or
  
• http://www.mdex.org.uk

The MDEX Consortium received funding from the UK Medical Research Council (MRC) and AVI BioPharma to perform a clinical trial to assess the safety and efficacy of the same drug utilised in the previous intramuscular study, but this time administered intravenously and repeatedly. This study was aimed at boys with Duchenne muscular dystrophy with mutations than can be rescued by the skipping of exon 51 [45-50; 47-50; 48-50; 49-50; 50; 52; 52-63].

This study, at GOSH (London) and the Royal Victoria Hospital (Newcastle) has now been successfully completed and data is being processed for submission to regulatory bodies in the US and Europe. The results of this study have been published in the Lancet ( 13;378:595-605, 2011). Briefly, the data showed (1) AVI-4658 was well tolerated in the trial and adverse events tended to be mild, transient and unrelated to the study drug, (2) all biopsies (12/12) at the four highest dose of 6 cohorts showed skipping of exon 51 in the dystrophin mRNA, a sign of systemic biologic activity, (3) all 8 patients in the two highest dose cohort and one other had increased dystrophin positive fibre counts, (4) first ever reported substantial de novo increase in dystrophin positive fibres (>50% of normal).

Both study sites are in the UK North Star Clinical network, which links 17 UK centres involved in the diagnosis and management of DMD and would welcome referral of patients for future trials.

• For more information visit the Clinical Trials website

A multi-centre multi-national trial with this study drug is recruiting DMD boys in UK at the Great Ormond Street Hospital(GOSH), London and at the Royal Victoria Infirmary, Newcastle.

It is a Phase lla, double blind, exploratory, parallel clinical trial to assess the optimal dose of GSK2402968 for safety, tolerability and efficacy, in ambulant patients with DMD.

The primary objective of this study is for efficacy of two different dosage regimens versus placebo and the secondary objectives of safety, tolerability, PK and long term efficacy.

It is planned to recruit up to 54 ambulant DMD boys from 5-7 centres aged at least 5 years and correctable by this study drug induced exon 51 skipping.

Recruitment to this study is now closed.

In a proportion of Duchenne muscular dystrophy boys the cause of the condition is the presence of nonsense mutations in the dystrophin gene.

PTC Therapeutics, USA has developed a drug PTC124, which can be taken by mouth and has the potential to reverse the genetic defect by resuming production of Dystrophin and thereby improve muscle development in these patients.

The preliminary findings from the Ataluren Study 007 did not show significant muscle improvement in the patients who participated in the study. The study was therefore discontinued. An update on this study was presented at the International Congress on Neuromuscular Diseases, Naples, Italy, 17-22 July 2010. Briefly, analysis showed that, on average, patients treated with low-dose ataluren experienced better outcomes on measures of efficacy than patients treated with high-dose ataluren or placebo - this phenomenon is not unique for ataluren and has been observed with other drugs for other diseases. Further analysis of efficacy data are ongoing. Discussions with regulatory bodies are ongoing regarding an extension study on eligible patients who participated in the primary trial.

A phase II, multicentre, randomised, adaptive, double-blind, placebo controlled study to assess safety and efficacy of olexosime (tro19622) in 3-25 year old Spinal Muscular Atrophy (SMA) patients.

This is a multi-centre, double-blind, randomized, placebo-controlled study in patients with SMA type 2 or non-ambulant type 3.

The study will be conducted in UK at GOSH London, Royal Victoria Hospital Newcastle and the Birmingham Heartland Hospital.

The study is sponsored by TROPHOS (a biopharmaceutical company based in France) and funded by AFM (Association Francaise contre les Myopathies).

The aim is to assess efficacy, futility, safety and tolerability of a new drug called olesoxime (TRO 19622).

This is a neuroprotective drug that acts by interacting with protein components of the mitochondrial permeability transition pore (mPTP), preventing the release of apoptotic factors and in turn neuronic death. Olesoxime has displayed an excellent safety profile and has been well tolerated in phase I clinical trials in healthy subjects. 

Recruitment to this study is now closed.

This is a double-blind randomised multi-centre, placebo-controlled trial of combined ACE-inhibitor and beta-blocker therapy in preventing the development of cardiomyopathy in genetically characterised males with DMD without echo-detectable left ventricular dysfunction.

It is a multi-centre study in the UK and is Sponsored by the Newcastle upon Tyne Hospitals NHS Foundation Trust. The study will recruit 140 eligible boys and its duration is 5 years.

Recruitment to this study is now open.