The purpose of this 2-part study is to assess the safety and efficacy of CORT113176 (dazucorilant) in patients with Amyotrophic Lateral Sclerosis (ALS).
In Part 1, eligible ALS patients will be randomized to one of three treatment arms (1:1:1) across North America and Europe for a 24-week double-blind treatment period. Patients who complete participation (i.e., completed all visits) in the double-blind treatment period will be eligible for participation in a 132-week open-label extension (OLE) study. A daily dose of 300 mg dazucorilant will be used in the 132-week OLE period. Patients who complete the double-blind treatment period and who do not enter the OLE will enter the 132-week follow-up period. In Part 2, eligible ALS patients will receive open-label treatment to evaluate dose titration and tolerability of dazucorilant. The dose titration will begin with an initial 75 mg once daily dose, and the dose will be titrated up as tolerated in 75 mg increments until the 300 mg once daily target dose is reached and maintained for 3 weeks. Patients who complete participation in the dose-titration treatment period will be eligible to continue treatment with dazucorilant 300 mg once daily in a 52-week open-label extension portion of the study.
Inclusion Criteria:
- Male and female patients ≥18 years of age with Sporadic or familial ALS. In Part 1,
patients must have a risk of ALS progression characterized by a European Network for
the Cure of ALS (ENCALS) risk profile score ≥ -6 and ≤ -3. In Part 2 patients must
have a risk of ALS progression characterized by an ENCALS risk profile score ≥ -7
and ≤ -3.
- If taking riluzole, edaravone, and/or sodium phenylbutyrate and taurursodiol, must
be on a stable dose prior to Screening. Sodium phenylbutyrate and taurursodiol are
not permitted for patients enrolled in Part 2 of the study.
- Part 2 only: Patients with a pathogenic mutation in superoxide dismutase 1 gene
(SOD1) must not be receiving treatment with tofersen or eligible for treatment with
tofersen if available. Patients who have received prior treatment with tofersen and
discontinued due to safety and/or efficacy reasons prior to Screening are eligible.
- Part 2 only: Use of ultra high-dose methylcobalamin for the treatment of ALS is
permitted provided the patient has been on a stable dose for ≥11 weeks prior to the
Day 1 visit.
Exclusion Criteria:
- History of a clinically significant non-ALS neurologic disorder
- Inability to swallow capsules.
- Blood platelet count <150,000/mm^3.
- Renal impairment indicated by Estimated Glomerular Filtration Rate (eGFR) ≤30
mL/min/1.73 m^2. Part 2 only: Patients with a recent history of acute kidney injury
should have returned to their baseline renal function prior to enrollment.
- Human immunodeficiency virus (HIV) or current chronic/active infection with
hepatitis C virus or hepatitis B virus. Part 2 only: Known history of HIV or
chronic/active infection with hepatitis C or hepatitis B virus; testing does not
need to be performed if infection status is unknown.
- Women who are pregnant, planning to become pregnant, or are breastfeeding.
- Use of non-invasive ventilation (NIV) or mechanical ventilation via tracheostomy, or
on any form of oxygen supplementation.
- Current or anticipated need of a diaphragm pacing system (DPS).
- Currently using glucocorticoids or have a history of regular systemic glucocorticoid
use within the last 12 months.
- Previous exposure or treatment with glucocorticoid receptor modulators or
antagonists.