Phase 2 trial testing dazucorilant in ALS patients now fully enrolled

Oral therapy aims to improve patients' ability to perform everyday tasks

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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The word 'Enrollment' is seen in black letters with 'Complete' written under it in red, with a zigzag line underneath.

A double-blind Phase 2 clinical trial that will test Corcept Therapeutics’ oral cortisol modulator dazucorilant against a placebo in people with amyotrophic lateral sclerosis (ALS) is now fully enrolled, the company announced in a press release.

Called DAZALS (NCT05407324), the trial involves 249 adults with sporadic or familial ALS across multiple sites in the U.S. and Canada, and in Europe.

Participants are randomly assigned to receive one of two dazucorilant doses (150 or 300 mg), or a placebo, with neither researchers nor patients knowing who gets which one. Treatment is given as four softgel capsules once daily for 24 weeks, or about six months, in addition to standard ALS treatments.

The trial’s main goals are to assess dazucorilant’s safety and tolerability, as well as changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, which measure a person’s ability to perform everyday tasks. The researchers also will evaluate changes in muscle strength, lung function, and quality of life after 24 weeks.

“Fully enrolling DAZALS is an important step toward understanding dazucorilant’s potential for significantly improving outcomes for people living with this devastating disease,”  said Bill Guyer, Corcept’s chief development officer. Early data from the trial is expected later this year, Guyer said.

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People with ALS often show signs of having overactive adrenal glands. These small glands, located atop the kidneys, are responsible for producing cortisol and other hormones.

Cortisol is a steroid hormone that is released into circulation in the body to help manage stressful conditions. However, prolonged elevations in cortisol levels can promote inflammation and nerve cell death, which is thought to drive ALS progression.

Consistently, high levels of cortisol seem to be particularly present in ALS patients with rapid disease progression.

Dazucorilant is a cortisol modulator that binds to glucocorticoid receptors to prevent their interaction with cortisol, preventing the cascade of events that cause neuronal inflammation and death. This is expected to reduce the negative effects of excessive cortisol in ALS patients.

In preclinical studies using animal models of ALS, the scientists found that daily treatment with dazucorilant eased inflammation and nerve cell death. Mice also had better motor function and less muscle wasting, as compared with untreated mice.

Now, Corcept aims to see if the therapy is safe and effective in humans at either of two doses.

Better treatments for ALS are urgently needed. … Dazucorilant showed great promise in an animal model of ALS – improving motor performance and reducing neuroinflammation and muscular atrophy.

The Phase 2 trial, now fully enrolled, has study sites in four U.S. states and eight European countries, as well as locations in Ontario and Quebec. Participants who complete the trial will then be eligible to enter an open-label extension study, in which they can receive a 300 mg daily dose of the active treatment for an additional 132 weeks, or about 2.5 years.

“Better treatments for ALS are urgently needed,” Guyer said, noting that “dazucorilant showed great promise in an animal model of ALS – improving motor performance and reducing neuroinflammation and muscular atrophy.”