Planning is currently underway for the world's first international multi-centre trial of a treatment for A-T. The Phase III trial aims to test the efficiency of the treatment in improving the neurological symptoms in children with A-T. If successful, this will be the first ever treatment which delivers a significant improvement in the major symptoms of A-T.
The treatment, which is called the EryDex System, involves a new technique of administering the steroid dexamethasone by encapsulating the drug into patient’s own red blood cells, which are then re-infused into the patient’s bloodstream. The drug is then released slowly but continuously from the red blood cells giving the clinical effect but without the serious side-effects normally found with the long-term use of steroids. The EryDex System process (encapsulation of Dexamethasone Sodium Phosphate into red blood cells) requires a special machine (see picture) and takes around one and a half hours. The red blood cells containg the encapsulated drug must be re-infused into the patient immediately. This infusion lasts approximately 40 minutes. This process must be repeated monthly.
This trial will involve testing the treatment in 180 patients of at least 6 years of age. This is a small number of participants for a Phase III trial, because A-T is such a rare condition, but it will still be a challenge to recruit. However, 22 centres in 14 countries all Continents (North America, Asia, Australia, Europe and Africa) have already agreed to participate.
Final details of the trial are currently being worked out. There will be some criteria that need to be met to participate. Those participating in the trial will need to be able to visit their centre at least once a month over the course of a year. Also as it is a placebo-controlled trial, not all participants will be receiving the investigational drug at the beginning of the trial, though by the end, everyone who completes the trial will have access to the drug on an open-label (that is you know that you are getting the drug) extension to the trial.
The A-T Society and the Paediatric A-T Centre in Nottingham have been working closely with the project for a number of years, both to help ensure that the trial goes ahead and that UK patients can participate.
The A-T Society is also part of a consortium of organisations which received a 6-million grant from the European Commission’s Horizon 2020 schemet o fundthe trial and related activities, which aim to better clarify some other aspects of the disease.
Background to the trial
A number of very small-scale studies in Italy suggested that when children with A-T were given the steroid drug Betamethasone, their neurological symptoms (movement, speech etc.) improved. However, people given steroids over a period of time develop serious side-effects, which prevented prolonged treatment.
Several years ago, researchers at the University of Urbino in central Italy developed this new technique for delivering the steroid dexamethasone, which is very similar to betamethasone, in a way which seemed likely to avoid these side effects. They set up the company Erydel to develop the EryDex System treatment.
In 2011-12 a small-scale Phase-II clinical trial of EryDex System was carried out in 22 patients in Italy, led by Prof. Luciana Chessa. Although it was not placebo-controlled (i.e. all participants received the drug) the trial showed both a statistically-significant improvement in neurological symptoms and an almost complete absence of the typical steroid side-effects. At the end of the trial, a number of patients were allowed to continue the treatment and over two years later have continued to be without side effects and seem to show some continued improvement.
The company have since been making arrangements to organise a large-scale Phase III trial. The FDA (the American Food and Drug Agency) have approved the proposed trial in principle, subject to a number of studies to establish the safety of the technique. The results of these have been now submitted and the company is now awaiting final authorisation to proceed with the trial.