Dazucorilante em pacientes com esclerose lateral amiotrófica (DAZALS) (DAZALS)
Um estudo de fase 2, multicêntrico, randomizado, duplo-cego, controlado por placebo, avaliando a segurança e a eficácia de CORT113176 (Dazucorilant) em pacientes com esclerose lateral amiotrófica (DAZALS)
The purpose of this 2-part study is to assess the safety and efficacy of CORT113176 (dazucorilant) in patients with Amyotrophic Lateral Sclerosis (ALS).
Visão geral do estudo
Status
Condições
Intervenção / Tratamento
Descrição detalhada
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.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Fase 2
Contactos e Locais
Locais de estudo
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Berlin, Alemanha, 13353
- 255
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Bonn, Alemanha, 53127
- 270
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Dresden, Alemanha, 1307
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Hanover, Alemanha, 30625
- 260
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Jena, Alemanha, 7747
- 265
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München, Alemanha, 81675
- 386
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Rostock, Alemanha, 18147
- 267
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Ulm, Alemanha, 89081
- 269
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Leuven, Bélgica, 3000
- 108
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Ontario
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Hamilton, Ontario, Canadá, L8N 3Z5
- 425
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Quebec
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Montreal, Quebec, Canadá, H3A2B4
- 273
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Barcelona, Espanha, 08003
- 302
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Barcelona, Espanha, 08035
- 115
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Madrid, Espanha, 28046
- 303
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Málaga, Espanha, 29010
- 282
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Valencia, Espanha, 46026
- 194
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Arizona
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Phoenix, Arizona, Estados Unidos, 85013
- 062
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California
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San Francisco, California, Estados Unidos, 94109
- 278
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New Jersey
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Neptune City, New Jersey, Estados Unidos, 07753
- 287
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New York
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New York, New York, Estados Unidos, 10032
- 353
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Bron, França, 69500
- 422
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Lille, França, 59037
- 258
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Limoges, França, 87042
- 257
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Marseille, França, 13385
- 261
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Montpellier, França, 42395
- 423
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Nice, França, 06001
- 259
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Paris, França, 75651
- 262
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Tours, França, 37000
- 256
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Utrecht, Holanda, 3584 CW
- 264
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Dublin, Irlanda, D09 YD60
- 253
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Bydgoszcz, Polônia, 85-163
- 283
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Krakow, Polônia, 30721
- 385
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Warsaw, Polônia, 01-684
- 254
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Warsaw, Polônia, 02-473
- 274
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Stoke-on-Trent, Reino Unido, ST4 6QG
- 263
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Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
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.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Triplo
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Part 1: CORT113176 (Dazucorilant) 300 mg
300 mg of dazucorilant will be administered once daily. |
300 mg of dazucorilant will be administered once daily in 4 capsules of 75 mg dazucorilant/capsule.
Outros nomes:
|
|
Experimental: Part 1: CORT113176 (Dazucorilant) 150 mg
150 mg of dazucorilant will be administered once daily. |
Dazucorilant and placebo will be administered once daily in 4 capsules, 2 capsules with 75 mg dazucorilant/capsule, and 2 capsules of placebo equivalent.
Outros nomes:
Placebo will be administered once daily in capsules of placebo equivalent. |
|
Comparador de Placebo: Part 1: Placebo (matched to study drug)
Placebo will be administered once daily. |
Placebo will be administered once daily in capsules of placebo equivalent. |
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Experimental: 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. |
Dazucorilant will be administered once daily in 75-mg capsules.
Outros nomes:
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O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
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Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
Prazo: Baseline to Week 24
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This outcome measure is assessed in study Part 1. |
Baseline to Week 24
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Incidence of Adverse Events (AEs), Serious Adverse Events (SAEs), treatment-related AEs, AEs by severity, and deaths due to AEs
Prazo: Baseline to Week 24
|
This outcome measure is assessed in study Part 1. |
Baseline to Week 24
|
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Incidence of treatment-emergent AEs and SAEs
Prazo: Baseline up to Week 12
|
This outcome measure is assessed in study Part 2. |
Baseline up to Week 12
|
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Incidence of treatment-emergent AEs leading to dose interruptions, dose reductions, and/or discontinuations of study drug
Prazo: Baseline up to Week 12
|
This outcome measure is assessed in study Part 2. |
Baseline up to Week 12
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Change from Baseline to Week 24 in muscle strength (assessed using hand-held dynamometer)
Prazo: Baseline to Week 24
|
This outcome measure is assessed in study Part 1. |
Baseline to Week 24
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Change from Baseline to Week 24 in Percent Slow Vital Capacity
Prazo: Baseline to Week 24
|
This outcome measure is assessed in study Part 1. |
Baseline to Week 24
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Change from Baseline to Week 24 in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Prazo: Baseline to Week 24
|
This outcome measure is assessed in study Part 1. |
Baseline to Week 24
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Time to Death
Prazo: From randomization date to the date of death from any cause up to 156 weeks
|
This outcome measure is assessed in study Part 1. |
From randomization date to the date of death from any cause up to 156 weeks
|
Colaboradores e Investigadores
Patrocinador
Investigadores
- Diretor de estudo: Sophia Majeed, PharmD, PhD, Corcept Therapeutics Incorporated
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Real)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
- Doenças do Sistema Nervoso Central
- Doenças do Sistema Nervoso
- Doenças Neuromusculares
- Doenças Metabólicas
- Doenças Neurodegenerativas
- Doenças da Medula Espinhal
- Proteinopatias TDP-43
- Deficiências de Proteostase
- Doença do neurônio motor
- Doenças Nutricionais e Metabólicas
- Esclerose Lateral Amiotrófica
- CORT113176
Outros números de identificação do estudo
- CORT113176-652
- 2021-005611-31 (Número EudraCT)
Plano para dados de participantes individuais (IPD)
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