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NCT05407324PHASE2Recruiting

Dazucorilant in Patients With Amyotrophic Lateral Sclerosis

Corcept Therapeutics

Start Date

11/15/2022

Completion Date

11/1/2027

Summary

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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.

Interventions

DRUG

Dazucorilant 300 mg

DRUG

Dazucorilant 150 mg

OTHER

Placebo

DRUG

Dazucorilant

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Conditions

Amyotrophic Lateral Sclerosis

Locations

062

Phoenix, Arizona 85013

United States

278

San Francisco, California 94109

United States

287

Neptune City, New Jersey 07753

United States

353

New York, New York 10032

United States

108

Leuven, 3000

Belgium

425

Hamilton, Ontario L8N 3Z5

Canada

273

Montreal, Quebec H3A2B4

Canada

422

Bron, 69500

France

258

Lille, 59037

France

257

Limoges, 87042

France

261

Marseille, 13385

France

423

Montpellier, 42395

France

259

Nice, 06001

France

262

Paris, 75651

France

256

Tours, 37000

France

255

Berlin, 13353

Germany

270

Bonn, 53127

Germany

268

Dresden, 1307

Germany

260

Hanover, 30625

Germany

265

Jena, 7747

Germany

386

München, 81675

Germany

267

Rostock, 18147

Germany

269

Ulm, 89081

Germany

253

Dublin, D09 YD60

Ireland

264

Utrecht, 3584 CW

Netherlands

283

Bydgoszcz, 85-163

Poland

385

Krakow, 30721

Poland

254

Warsaw, 01-684

Poland

274

Warsaw, 02-473

Poland

302

Barcelona, 08003

Spain

115

Barcelona, 08035

Spain

303

Madrid, 28046

Spain

282

Málaga, 29010

Spain

194

Valencia, 46026

Spain

263

Stoke-on-Trent, ST4 6QG

United Kingdom