Phase 2 Trial Will Test Cortisol Modulator Dazucorilant in ALS

The DAZALS Phase 2 study will enroll patients in the US and Europe

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Dazucorilant, Corcept Therapeutics‘ investigational cortisol modulator for people with amyotrophic lateral sclerosis (ALS), is being evaluated in a Phase 2 clinical trial.

The DAZALS Phase 2 study (NCT05407324) aims to determine dazucorilant’s safety and efficacy against a placebo in about 198 adults with ALS.

It will be conducted in collaboration with the Treatment Research Initiative to Cure ALS (TRICALS), a large European network of leading ALS experts, patients, and patient advocacy groups dedicated to finding ALS treatments. Enrollment will take place at yet-undisclosed sites in Europe and the U.S.; more information about contacts and locations will be available here.

“ALS, also known as Lou Gehrig’s disease, is a devastating neuromuscular illness with an urgent need for better treatment,” Bill Guyer, Corcept Therapeutics’ chief development officer, said in a press release. “We are excited to initiate this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe.”

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The study’s design was presented in a poster titled,”DAZALS: A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Of Dazucorilant In Patients With Amyotrophic Lateral Sclerosis,” at the European Network to Cure ALS (ENCALS) meeting.

Increased levels of cortisol, the body’s primary stress hormone, have been observed in ALS patients, particularly those with rapid disease progression. Prolonged exposure to cortisol has negative consequences, including increased inflammation and toxicity to nerve cells, that could work to drive ALS progression.

Dazucorilant is an oral small molecule that works by blocking the glucocorticoid receptor, which initiates a series of molecular reactions upon binding to cortisol. In doing so, the treatment is thought to block the negative consequences of cortisol exposure and slow disease progression.

In a mouse model of ALS, daily dazucorilant treatment reduced signs of inflammation and prevented nerve cell death. Mice given the therapy also demonstrated improved motor function and reduced muscle shrinkage (atrophy).

“Dazucorilant showed great promise in animal models of ALS — improving motor performance and reducing neuroinflammation and muscular atrophy,” said Leonard van den Berg, MD, PhD, TRICALS chairman and professor of neurology at the University Medical Center Utrecht, Netherlands.

ENCALS profile score

Patient eligibility for DAZALS will be determined using the ENCALS risk profile score, which sums up seven characteristics into a single score, ranging from about –12 to zero, that estimates a patient’s overall prognosis.

Patients with an ENCALS scores of –6 to –3 are eligible for DAZALS, which accounts for about 57.7% of the overall ALS population. The goal is to obtain a group of patients with a similar disease profile, excluding patients with either very slow (lower scores) or very fast (higher scores) disease progression.

DAZALS participants will be assigned randomly to one of two dazucorilant doses (150 or 300 mg) or a placebo, once daily for 24 weeks (about six months). Participants also may continue to receive their ALS medications while on the trial.

The medication will be provided in softgel capsules containing 75 mg of the medication. At each dosing, all participants will take four capsules. All four will contain the active medication for the 300 mg group, two will have active medication, and two will have placebo for the 150 mg group, and all four will contain placebo in the placebo group.

Participants who complete the six-month treatment period will have the option of enrolling in the trial’s open-label extension period, in which all will receive the 300 mg dose for an additional 24 weeks.

Study goals

The study’s main goals are to assess the treatment’s safety and changes in functional declines, as assessed by the ALS-Functional Rating Scale — Revised (ALSFRS-R). Secondary measures include changes in muscle strength, lung function, quality of life, and time to any event — including death, ALS-related hospitalization, or need for respiratory support.

Three weeks after starting treatment, blood samples will be collected in about 20% of patients  for an exploratory pharmacokinetic analysis, which will assess how the treatment moves into, through, and out of the body. Additional exploratory goals include blood levels of ALS-related biomarkers and patient-reported outcomes.

“I am excited to partner with Corcept to study dazucorilant’s potential to significantly improve treatment outcomes for people living with ALS,” van den Berg said.