A Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Evaluating Safety and Efficacy of CORT113176 (Dazucorilant) in Patients With Amyotrophic Lateral Sclerosis (DAZALS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 279
- 试验地点
- 35
- 主要终点
- Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
研究概览
简要总结
The purpose of this 2-part study is to assess the safety and efficacy of CORT113176 (dazucorilant) in patients with Amyotrophic Lateral Sclerosis (ALS).
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 ≤ -
- •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 ≤ -
- •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.
排除标准
- •History of a clinically significant non-ALS neurologic disorder
- •Inability to swallow capsules.
- •Blood platelet count <150,000/mm^
- •Renal impairment indicated by Estimated Glomerular Filtration Rate (eGFR) ≤30 mL/min/1.73 m^
- •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.
研究组 & 干预措施
Part 1: CORT113176 (Dazucorilant) 150 mg
150 mg of dazucorilant will be administered once daily.
干预措施: Placebo (Other)
Part 1: Placebo (matched to study drug)
Placebo will be administered once daily.
干预措施: Placebo (Other)
Part 1: CORT113176 (Dazucorilant) 300 mg
300 mg of dazucorilant will be administered once daily.
干预措施: Dazucorilant 300 mg (Drug)
Part 1: CORT113176 (Dazucorilant) 150 mg
150 mg of dazucorilant will be administered once daily.
干预措施: Dazucorilant 150 mg (Drug)
Part 2: CORT113176 (Dazucorilant) 75 - 300 mg Dose-titration
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.
干预措施: Dazucorilant (Drug)
结局指标
主要结局
Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
时间窗: Baseline to Week 24
This outcome measure is assessed in study Part 1.
Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, AEs by severity, and deaths due to AEs
时间窗: Baseline to Week 24
This outcome measure is assessed in study Part 1.
Incidence of treatment-emergent AEs and SAEs
时间窗: Baseline up to Week 12
This outcome measure is assessed in study Part 2.
Incidence of treatment-emergent AEs leading to dose interruptions, dose reductions, and/or discontinuations of study drug
时间窗: Baseline up to Week 12
This outcome measure is assessed in study Part 2.
Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
时间窗: Baseline to Week 24
This outcome measure is assessed in study Part 1.
次要结局
- Change from Baseline to Week 24 in muscle strength (assessed using hand-held dynamometer)(Baseline to Week 24)
- Change from Baseline to Week 24 in Percent Slow Vital Capacity(Baseline to Week 24)
- Change from Baseline to Week 24 in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)(Baseline to Week 24)
- Time to Death(From randomization date to the date of death from any cause up to 156 weeks)
- Change from Baseline to Week 24 in Percent Slow Vital Capacity(Baseline to Week 24)
- Change from Baseline to Week 24 in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)(Baseline to Week 24)
- Time to Death(From randomization date to the date of death from any cause up to 156 weeks)