A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Safety and Efficacy of CORT113176 (Dazucorilant) in Patients with Amyotrophic Lateral Sclerosis (DAZALS)

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 15

Inclusion Criteria

1. Male and female patients >=18 years of age with ALS as defined by Gold Coast
Criteria.
2. Patients with sporadic or familial ALS with a risk of ALS progression
characterized by an ENCALS risk profile score >=-6 and <= -3.
3.Regulatory-authority-approved therapies for the treatment of ALS are
permitted. If taking riluzole and/or edaravone, and/or sodium phenylbutryte
and taurursodial, must have been on a stable dose of riluzole for >=30 days
and/or edaravone for >=60 days and/or sodium phenylbutyrate and taurursodial
maintenance dosage >=30 days prior to Screening.
4. Medically able to undergo the study procedures and to adhere to the visit
schedule at the time of study entry, as determined by the Investigator.
5. Able to understand the purpose and risks of the study; willing and able to
adhere to scheduled visits, treatment plans, laboratory tests, and other study
evaluations and procedures.
6. Provide written informed consent for participation in the study.
7. Male patients and female patients of childbearing potential must agree to
use a protocol-specified method of contraception from screening and during the
study until 28 days after last dose of study drug.

Exclusion Criteria

1. History of a clinically significant non-ALS neurologic disorder, including,
but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy,
inherited neuropathies, Alzheimer*s disease, cervical spondylosis, Parkinson*s
disease, Lewy body dementia, vascular dementia, Huntington*s disease, epilepsy,
stroke, multiple sclerosis, multifocal motor neuropathy, diabetic neuropathy,
brain tumor, or brain infection/abscess. 2. Inability to swallow capsules. 3.
Blood platelet count <150,000/mm3. 4. Renal impairment indicated by eGFR <=30
mL/min/1.73m2. 5. Human immunodeficiency virus (HIV) or current chronic/active
infection with hepatitis C virus or hepatitis B virus including patients with
chronic or active hepatitis B as diagnosed by serologic tests. 6. Women who are
pregnant, planning to become pregnant, or are breastfeeding. Women of
childbearing potential who are unwilling or unable to use highly effective
method of contraception from screening through the duration of treatment and up
to 28 days after last dose of study drug. 7. Known liver impairment (Child-Pugh
Class A, B, or C). 8. History of Class III/IV heart failure (per New York Heart
Association). 9. At the time of Screening, any use of non-invasive ventilation
(NIV), e.g., continuous positive airway pressure [CPAP], noninvasive bi-level
positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any
portion of the day, or mechanical ventilation via tracheostomy, or on any form
of oxygen supplementation. 10. Any form of cancer within the 5 years before
first dose in this study (with the exception of basal cell and/or squamous cell
cancer of the skin that has been treated completely and is without evidence of
local recurrence or metastasis). 11. History of any other clinically
significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory,
gastrointestinal (GI), bleeding, autoimmune, neurological, psychiatric
disorder, or unstable medical condition (other than ALS), as judged by the
Investigator. 12. History and/or symptoms of adrenal insufficiency. 13.
Abnormal liver function defined as aspartate aminotransferase (AST) or alanine
aminotransferase (ALT) >3 × upper limit of normal (ULN). 14. QTcF interval
based on the mean of 2 ECGs of >450 ms, for men and >470 ms for women. 15.
History of additional risk factors for torsades de pointes (e.g., heart
failure, hypokalemia, family history of long-QT syndrome). 16. Positive
nasopharyngeal PCR test for SARS-CoV-2 on Day -1 or within 8 weeks prior to
Screening. 17. Ongoing use of any strong CYP3A4 inhibitor/inducer or any
medication with a narrow therapeutic index that is predominantly metabolized by
CYP2C8. 18. Taking, or have taken, any strong CYP3A inducer within 30 days (or
5 half-lives if longer) before Screening, or any strong CYP3A inhibitor within
14 days before Screening. 19. Current or anticipated need, in the opinion of
the Investigator, of a diaphragm pacing system (DPS) during the study period.
20. Received any live or attenuated vaccine within 30 days, before the first
dose of study drug. Exceptions may apply on a case-by-case basis, if considered
not to interfere with the objectives of the study, as agreed by the PI and the
Corcept Medical Monitor. 21. Currently using glucocorticoids or have a history
of r

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary Efficacy Endpoint<br /><br>• Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised<br /><br>(ALSFRS-R) total<br /><br>score.<br /><br><br /><br>Primary Safety Endpoint<br /><br>• Incidence of AEs, SAEs, treatment-related AEs, AEs by severity, and deaths<br /><br>due to AEs.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• Change from Baseline to Week 24 in muscle strength (assessed using hand-held<br /><br>dynamometer).<br /><br>• Change from Baseline to Week 24 in:<br /><br>* Percent Slow Vital Capacity<br /><br>* EQ-5D-5L.<br /><br>• Time to death.<br /><br>• Time to respiratory support >22 hours per day for 7 days.<br /><br>• Time to death or time to respiratory support >22 hours per day for 7 days.<br /><br>• Combined Assessment of Function and Survival (CAFS).<br /><br>• Plasma samples for pharmacokinetic (PK) analysis will be obtained in a<br /><br>dedicated PK substudy in a subset (~20%) of patients at the Week 3 visit. The<br /><br>dazucorilant AUC and Cmax will be reported.</p><br>