Dazucorilant in Patients With Amyotrophic Lateral Sclerosis

Official title

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

Overview

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

Detailed 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., complete 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 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.

Interventions

• Drug Dazucorilant 300 mg
  300 mg of dazucorilant will be administered once daily in 4 capsules of 75 mg dazucorilant/capsule.
• Drug Dazucorilant 150 mg
  Dazucorilant and placebo will be administered once daily in 4 capsules, 2 capsules with 75 mg dazucorilant/capsule, and 2 capsules of placebo equivalent.
• Other Placebo
  Placebo will be administered once daily in capsules of placebo equivalent.
• Drug Dazucorilant
  Dazucorilant will be administered once daily in 75-mg capsules.

Primary outcome measures

• Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score. [Time frame: Baseline to Week 24]
• Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, AEs by severity, and deaths due to AEs [Time frame: Baseline to Week 24]
• Incidence of treatment-emergent AEs and SAEs [Time frame: Baseline up to Week 12]
• Incidence of treatment-emergent AEs leading to dose interruptions, dose reductions, and/or discontinuations of study drug [Time frame: Baseline up to Week 12]

Secondary outcome measures (4)

• Change from Baseline to Week 24 in muscle strength (assessed using hand-held dynamometer) [Time frame: Baseline to Week 24]
• Change from Baseline to Week 24 in Percent Slow Vital Capacity [Time frame: Baseline to Week 24]
• Change from Baseline to Week 24 in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) [Time frame: Baseline to Week 24]
• Time to Death [Time frame: From randomization date to the date of death from any cause up to 156 weeks]

Eligibility criteria

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 Treatment Research Initiative to Cure ALS (TRICALS) 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 (i.e, eGFR prior to acute kidney injury) 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.
• Cancer that is currently being treated (except adequately controlled basal cell carcinoma or squamous cell carcinoma of the skin, stage I endometrial cancer or carcinoma in situ of the cervix or breast) or a history of cancer with an expected survival < 2 years.
• Current or anticipated need of a diaphragm pacing system (DPS).
• Previous exposure or treatment with glucocorticoid receptor modulators or antagonists.
• Taking, or have taken, any systemic, inhaled, or potent dermatologic topical corticosteroids (Class I to III) within a period equivalent to 5 half-lives of the corticosteroid used prior to first dose of study drug. Patients who have stopped glucocorticoid use should have an alternative option if their condition deteriorates during the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

France · 8 centers

• 422 — Bron
• 258 — Lille
• 257 — Limoges
• 261 — Marseille
• 423 — Montpellier
• 259 — Nice
• 262 — Paris
• 256 — Tours

Germany · 8 centers

• 255 — Berlin
• 270 — Bonn
• 268 — Dresden
• 260 — Hanover
• 265 — Jena
• 386 — München
• 267 — Rostock
• 269 — Ulm

Spain · 5 centers

• 302 — Barcelona
• 115 — Barcelona
• 303 — Madrid
• 282 — Málaga
• 194 — Valencia

United States · 4 centers

• 062 — Phoenix
• 278 — San Francisco
• 287 — Neptune City
• 353 — New York

Poland · 4 centers

• 283 — Bydgoszcz
• 385 — Krakow
• 254 — Warsaw
• 274 — Warsaw

Canada · 2 centers

• 425 — Hamilton
• 273 — Montreal

Belgium · 1 center

• 108 — Leuven

Ireland · 1 center

• 253 — Dublin

Netherlands · 1 center

• 264 — Utrecht

United Kingdom · 1 center

• 263 — Stoke-on-Trent

Identifiers

NCT: NCT05407324 · CORT113176-652 · 2021-005611-31

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗