Dazucorilant hos pasienter med amyotrofisk lateral sklerose (DAZALS) (DAZALS)
En fase 2, multisenter, randomisert, dobbeltblind, placebokontrollert studie som evaluerer sikkerhet og effekt av CORT113176 (Dazucorilant) hos pasienter med amyotrofisk lateral sklerose (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).
Studieoversikt
Status
Forhold
Intervensjon / Behandling
Detaljert beskrivelse
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.
Studietype
Registrering (Antatt)
Fase
- Fase 2
Kontakter og plasseringer
Studiesteder
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Leuven, Belgia, 3000
- 108
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Ontario
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Hamilton, Ontario, Canada, L8N 3Z5
- 425
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Quebec
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Montreal, Quebec, Canada, H3A2B4
- 273
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Arizona
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Phoenix, Arizona, Forente stater, 85013
- 062
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California
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San Francisco, California, Forente stater, 94109
- 278
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New Jersey
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Neptune City, New Jersey, Forente stater, 07753
- 287
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New York
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New York, New York, Forente stater, 10032
- 353
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Bron, Frankrike, 69500
- 422
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Lille, Frankrike, 59037
- 258
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Limoges, Frankrike, 87042
- 257
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Marseille, Frankrike, 13385
- 261
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Montpellier, Frankrike, 42395
- 423
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Nice, Frankrike, 06001
- 259
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Paris, Frankrike, 75651
- 262
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Tours, Frankrike, 37000
- 256
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Dublin, Irland, D09 YD60
- 253
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Utrecht, Nederland, 3584 CW
- 264
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Bydgoszcz, Polen, 85-163
- 283
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Krakow, Polen, 30721
- 385
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Warsaw, Polen, 01-684
- 254
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Warsaw, Polen, 02-473
- 274
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Barcelona, Spania, 08003
- 302
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Barcelona, Spania, 08035
- 115
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Madrid, Spania, 28046
- 303
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Málaga, Spania, 29010
- 282
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Valencia, Spania, 46026
- 194
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Stoke-on-Trent, Storbritannia, ST4 6QG
- 263
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Berlin, Tyskland, 13353
- 255
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Bonn, Tyskland, 53127
- 270
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Dresden, Tyskland, 1307
- 268
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Hanover, Tyskland, 30625
- 260
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Jena, Tyskland, 7747
- 265
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München, Tyskland, 81675
- 386
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Rostock, Tyskland, 18147
- 267
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Ulm, Tyskland, 89081
- 269
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Deltakelseskriterier
Kvalifikasjonskriterier
Alder som er kvalifisert for studier
Tar imot friske frivillige
Kjønn som er kvalifisert for studier
Beskrivelse
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.
Studieplan
Hvordan er studiet utformet?
Designdetaljer
- Primært formål: Behandling
- Tildeling: Randomisert
- Intervensjonsmodell: Parallell tildeling
- Masking: Trippel
Våpen og intervensjoner
Deltakergruppe / Arm |
Intervensjon / Behandling |
|---|---|
|
Eksperimentell: 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.
Andre navn:
|
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Eksperimentell: 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.
Andre navn:
Placebo will be administered once daily in capsules of placebo equivalent. |
|
Placebo komparator: 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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Eksperimentell: 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.
Andre navn:
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Hva måler studien?
Primære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
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Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score.
Tidsramme: 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
Tidsramme: 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
Tidsramme: Baseline up to Week 12
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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
Tidsramme: Baseline up to Week 12
|
This outcome measure is assessed in study Part 2. |
Baseline up to Week 12
|
Sekundære resultatmål
Resultatmål |
Tiltaksbeskrivelse |
Tidsramme |
|---|---|---|
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Change from Baseline to Week 24 in muscle strength (assessed using hand-held dynamometer)
Tidsramme: 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
Tidsramme: 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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Change from Baseline to Week 24 in EuroQol-5 Dimensions-5 Levels (EQ-5D-5L)
Tidsramme: Baseline to Week 24
|
This outcome measure is assessed in study Part 1. |
Baseline to Week 24
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Time to Death
Tidsramme: From randomization date to the date of death from any cause up to 156 weeks
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This outcome measure is assessed in study Part 1. |
From randomization date to the date of death from any cause up to 156 weeks
|
Samarbeidspartnere og etterforskere
Sponsor
Etterforskere
- Studieleder: Sophia Majeed, PharmD, PhD, Corcept Therapeutics Incorporated
Studierekorddatoer
Studer hoveddatoer
Studiestart (Faktiske)
Primær fullføring (Antatt)
Studiet fullført (Antatt)
Datoer for studieregistrering
Først innsendt
Først innsendt som oppfylte QC-kriteriene
Først lagt ut (Faktiske)
Oppdateringer av studieposter
Sist oppdatering lagt ut (Faktiske)
Siste oppdatering sendt inn som oppfylte QC-kriteriene
Sist bekreftet
Mer informasjon
Begreper knyttet til denne studien
Nøkkelord
Ytterligere relevante MeSH-vilkår
Andre studie-ID-numre
- CORT113176-652
- 2021-005611-31 (EudraCT-nummer)
Plan for individuelle deltakerdata (IPD)
Planlegger du å dele individuelle deltakerdata (IPD)?
Legemiddel- og utstyrsinformasjon, studiedokumenter
Studerer et amerikansk FDA-regulert medikamentprodukt
Studerer et amerikansk FDA-regulert enhetsprodukt
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