Dazucorilant in Patients With Amyotrophic Lateral Sclerosis (DAZALS)

Corcept Therapeutics

Status and phase: Active, not recruiting; Phase 2

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: Dazucorilant; Other: Placebo; Drug: Dazucorilant 150 mg; Drug: Dazucorilant 300 mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05407324

2021-005611-31 (EudraCT Number)

CORT113176-652

Details and patient eligibility

About

The purpose of this 2-part study is to assess the safety and efficacy of CORT113176 (dazucorilant) in patients with Amyotrophic Lateral Sclerosis (ALS).

Full description

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.

Enrollment: 279 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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279 participants in 4 patient groups, including a placebo group

Part 1: CORT113176 (Dazucorilant) 300 mg

Experimental group

Description:

300 mg of dazucorilant will be administered once daily.

Treatment:

Drug: Dazucorilant 300 mg

Part 1: CORT113176 (Dazucorilant) 150 mg

Experimental group

Description:

150 mg of dazucorilant will be administered once daily.

Treatment:

Drug: Dazucorilant 150 mg

Other: Placebo

Part 1: Placebo (matched to study drug)

Placebo Comparator group

Description:

Placebo will be administered once daily.

Treatment:

Other: Placebo

Part 2: CORT113176 (Dazucorilant) 75 - 300 mg Dose-titration

Experimental group

Description:

75 mg of dazucorilant will be administered once daily for 1 week, and increased weekly in 75 mg increments up to 300 mg once daily.

Treatment:

Drug: Dazucorilant