Phase 2 trial of cortisol modulator for ALS still enrolling patients

Corcept to test safety, efficacy of its therapy dazucorilant in US, EU

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Enrollment is still ongoing for a Phase 2 clinical trial testing the safety and efficacy of Corcept Therapeutics‘ cortisol modulator, called dazucorilant, in people with amyotrophic lateral sclerosis (ALS).

The DAZALS trial (NCT05407324), launched in November 2022, is expected to enroll an estimated 198 adults with sporadic or familial ALS across multiple sites in the U.S. and Europe. Recruitment is now underway at three locations in the Netherlands and Poland, with more sites expected to open soon.

The study is being conducted in partnership with the Treatment Research Initiative to Cure ALS (TRICALS), a European network focused on finding new treatments for the progressive neurodegenerative disease.

“The 55,000 patients in the United States and Europe with ALS have an urgent need for better treatment,” Bill Guyer, Corcept’s chief development officer, said in a company press release.

“We are conducting this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe, to investigate dazucorilant’s potential to significantly improve the lives of patients with ALS,” Guyer added.

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Up to 198 adults needed for DAZALS trial

Many people with ALS show symptoms of overactive adrenal glands, which are the small glands that sit atop the kidneys. Such signs can include high levels of the stress hormone cortisol and irregular circadian rhythms, commonly known as one’s biological clock.

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

Dazucorilant is an antagonist of the glucocorticoid receptors, meaning it prevents cortisol from binding its natural receptors in the body and initiating the cascade of events leading to neuronal inflammation and death. It use is expected to ease the harmful effects of excess cortisol.

In preclinical studies, daily treatment with dazucorilant was found to reduce inflammation and protect against nerve cell death in animal models of ALS. Mice on the therapy also had better motor function and less muscle wasting than untreated mice.

“Dazucorilant showed great promise in animal models of ALS — improving motor performance and reducing neuroinflammation and muscular atrophy,” Guyer said.

The ongoing DAZALS trial is designed to test dazucorilant’s safety and efficacy in adults, 18 and older, with moderate rates of ALS disease progression.

We are conducting this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe, to investigate dazucorilant’s potential to significantly improve the lives of patients with ALS.

To determine whether patients are eligible, their overall prognosis will be estimated using a tool called the European Network to Cure ALS (ENCALS) risk profile score, whose scores ranges from about -12 to zero. Scores closer to zero indicate patients with very fast progression and short survival times, while those closer to minus 12 are given to those with very slow progression with good prognosis and survival rates.

The DAZALS trial is including patients with scores raging from –6 to –3, a range that includes nearly 60% of the overall ALS population and selects patients with similar disease progression rates.

Participants will be assigned randomly to one of two dazucorilant doses (150 mg or 300 mg) or a placebo, given as softgel capsules once daily for 24 weeks, or about six months.

The trial’s main goals are to determine the treatment’s safety, as well as changes in the ability to perform day-to-day tasks, as assessed with the ALS Functional Rating Scale Revised (ALSFRS-R). Researchers also will investigate changes in muscle strength, lung function, and quality of life as secondary outcome measures.

After completing the clinical trial, patients will have the option for enrollment in an open-label extension part, in which all will receive the 300 mg dose for an additional 24 weeks.