A new clinical trial, investigating Dazucorilant, for the treatment of MND is now open for recruitment in the UK. With this trial, there are now 6 clinical trials recruiting in the UK, further highlighting the current momentum in finding potential effective treatments for MND.
People living with MND often show signs of over-active adrenal glands, with symptoms including high levels of the stress hormone, called cortisol. Studies have shown that high levels of cortisol promote inflammation and nerve cell death. Both of which are thought to contribute to the development of MND. Researchers hope that Dazucorilant will reduce the negative consequences of increased cortisol levels and protect against nerve cell death.
What is cortisol?
Cortisol is a hormone which affects almost every organ and tissue in the body. It plays an important role in:
- Regulating the body’s stress response – it can help the body stay on high alert and provide energy to the body during times of stress.
- Regulating metabolism – making sure fats, proteins and carbohydrates are used properly in the body.
- Boost the immune system – by reducing inflammation within the body.
If the levels of cortisol are too high or too low, especially for extended periods of time, this can be bad for the overall health of a person.
What happens in MND?
As just mentioned, having too high or low levels of cortisol can play havoc in the body. In people living with MND, elevated levels of cortisol have been observed, particularly in the morning upon waking. These continued high levels can start to damage the immune system and cause increased inflammation in the brain and central nervous system.
Inflammation is part of the body’s way of protecting itself when it has been exposed to damage or attack from bacteria or viruses. However, sometimes inflammation can become counterproductive. This results in an attack on the body’s own cells and tissues. Studies have shown that when this inflammatory attack happens in MND, motor neurones are also damaged and die.
How is Dazucorilant thought to work?
The pharmaceutical company behind Dazucorilant, called Corcept, have theorised that reducing the effects of excess cortisol could benefit people living with MND and reduce neurodegeneration.
Throughout the body there are receptors, known as glucocorticoid receptors, which cortisol binds to. Dazucorilant competes with cortisol for these receptors which results in less cortisol being able to bind. Cortisol levels within the body are then reduced, limiting the negative impacts of excessive cortisol. It is hoped that reducing the cortisol levels will reduce neuronal death.
Before a potential new treatment is tested in humans, it is often tested in models of MND to make sure that it is safe and to see if it could have any benefit for people living with MND. Dazucorilant was tested in a model of sporadic MND, which included increased levels of cortisol. They found that after 21 days of treatment, inflammation was reduced. Dazucorilant also helped to protect nerve cells from death.
These promising pre-clinical results have now led to the development of a phase 2 clinical trial to investigate the use of Dazucorilant in people living with MND.
A new phase 2 MND clinical trial
A phase 2 clinical trial, known as DAZALS, is currently underway to test Dazucorilant in people living with MND. The aim is to evaluate the safety and efficacy of Dazucorilant by recruiting 198 participants across sites in Europe and the United States. The trial is randomised, double-blind and placebo-controlled. This means participants will be randomly placed into either the treatment or placebo group and neither the researcher nor the participant will know which group they are in.
This trial is looking to recruit participants who have a similar disease progression. They will determine who is eligible for the trial by using a tool called the European Network to Cure ALS (ENCALS) risk profile score. This score takes into account 7 different characteristics from a person living with MND to better estimate their prognosis. The score ranges from -12 to zero. Scores close to zero suggest very fast progression and short survival times, and scores close to -12 suggest very slow progression and longer survival times.
To be eligible for the trial participants will need to have a score ranging from -six to -three. This means that around 60% of the overall MND population would be eligible for this trial. Previous research showed, on average, 60% of people living with MND are excluded from clinical trials. The DAZALS trial will give more people an opportunity to take part in research and access a clinical trial.
In addition to increasing the number of people eligible for the trial, DAZALS will also recruit more people in the treatment group of the trial compared to the placebo (in a 2:1 ratio). The trial is also investigating different doses of Dazucorilant. Participants randomised into the treatment group will either receive 150 mg or 300 mg. The placebo-controlled phase of the trial will run for 24-weeks, where participants will receive either the treatment or placebo. Then all participants will have the opportunity to enter the open-label extension and receive Dazucorilant for a further 24-weeks.
Design of the DAZALS trial
How can I get involved in the trial?
DAZALS is a multi-centre trial which will recruit participants in Europe and the United States. It is currently recruiting in the UK at the following site:
- Royal Stoke University Hospital. Please contact thomas.lambert@uhnm.nhs.uk to register your interest to take part in the trial.
RELATED TOPIC
Website | Clinical Trials
Find out about treatment trials recruiting in the UK
Going forward
The pre-clinical data and proposed mechanism for Dazucorilant looks promising, but it is important to now wait for the results of this phase 2 clinical trial. We will continue to follow its progress as it moves through recruitment and dosing and will keep the MND community informed.
* The information in this blog was correct at the time of publication.
