A SUPER-powered WP Engine Atlas Test Site

Joe&#039;s Atlas Experimentation Site

A double-blind Phase 2 clinical trial that will test Corcept Therapeutics&#8217; oral <a href="https://corcept.com/cortisolmodulation/">cortisol modulator</a> dazucorilant against a placebo in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS) is now fully enrolled, the company announced in a <a href="https://www.globenewswire.com/news-release/2024/04/15/2862710/0/en/Corcept-Completes-Enrollment-in-Phase-2-DAZALS-Trial-in-Patients-With-Amyotrophic-Lateral-Sclerosis-ALS.html">press release</a>.
Called <a href="https://clinicaltrials.gov/study/NCT05407324">DAZALS (NCT05407324)</a>, the trial involves 249 adults with <a href="https://alsnewstoday.com/forms-of-als/">sporadic or familial ALS</a> 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 <a href="https://alsnewstoday.com/als-treatment/">ALS treatments</a>.
The trial&#8217;s main goals are to assess dazucorilant&#8217;s safety and tolerability, as well as changes in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, which measure a person&#8217;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&#8217;s potential for significantly improving outcomes for people living with this devastating disease,”  said Bill Guyer, <a href="https://corcept.com/">Corcept</a>’s chief development officer. Early data from the trial is expected later this year, Guyer said.
[recommended-reading id=90892]
<h3>Fully enrolled human trial follows positive results in animal study</h3>
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 <a href="https://alsnewstoday.com/stages-of-als/">disease progression</a>.
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 <a href="https://www.sciencedirect.com/science/article/abs/pii/S0006899319306055">preclinical studies</a> 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.
[quote=&#8221;center&#8221;]Better treatments for ALS are urgently needed. &#8230; Dazucorilant showed great promise in an animal model of ALS – improving motor performance and reducing neuroinflammation and muscular atrophy.[/quote]
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.”

Phase 2 trial testing dazucorilant in ALS patients now fully enrolled

Enrollment is still ongoing for a Phase 2 clinical trial testing the safety and efficacy of <a href="https://www.corcept.com">Corcept Therapeutics</a>&#8216; cortisol modulator, called dazucorilant, in people with <a href="https://alsnewstoday.com/what-is-als/">amyotrophic lateral sclerosis</a> (ALS).
The <a href="https://clinicaltrials.gov/ct2/show/NCT05407324">DAZALS trial (NCT05407324)</a>, launched in November 2022, is expected to enroll an estimated 198 adults with <a href="https://alsnewstoday.com/forms-of-als/">sporadic or familial ALS</a> across multiple sites in the U.S. and Europe. Recruitment is <a href="https://clinicaltrials.gov/ct2/show/NCT05407324#contactlocation">now underway</a> at three locations in the Netherlands and Poland, with more sites expected to open soon.
The study is being conducted in partnership with the <a href="https://www.tricals.org/en/">Treatment Research Initiative to Cure ALS</a> (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 <a href="https://www.globenewswire.com/news-release/2023/02/28/2617676/0/en/Corcept-Therapeutics-Announces-Fourth-Quarter-and-Full-Year-2022-Audited-Financial-Results-and-Provides-Corporate-Update.html">company press release</a>.
“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.
[recommended-reading id=79333]
<h3>Up to 198 adults needed for DAZALS trial</h3>
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&#8217;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 <a href="https://alsnewstoday.com/causes-of-als/">development of ALS</a>.
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 <a href="https://www.sciencedirect.com/science/article/abs/pii/S0006899319306055">protect against nerve cell death</a> 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&#8217;s safety and efficacy in adults, 18 and older, with moderate rates of ALS disease progression.
[quote align=&#8221;center&#8221;]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.[/quote]
To determine <a href="https://alsnewstoday.com/news/corcept-therapeutics-phase-2-trial-dazucorilant-als/">whether patients are eligible</a>, 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&#8217;s main goals are to determine the treatment&#8217;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.

Tag: Dazucorilant

Phase 2 trial testing dazucorilant in ALS patients now fully enrolled

Phase 2 trial of cortisol modulator for ALS still enrolling patients