A study into the efficacy and safety of dazucorilant (CORT113176) in patients with Amyotrophic Lateral Sclerosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Corcept Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

4 Nov 2022 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Corcept Therapeutics Incorporated

External identifiers

EU CT number

2024-514082-19-00

EudraCT number

2021-005611-31

ClinicalTrials.gov

NCT05407324

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Pharmacodynamic, Efficacy

Part 1: Double-Blind, Randomized Arms:
- To assess the efficacy of dazucorilant in patients with ALS
- To assess the safety of dazucorilant in patients with ALS
Part 2: Open-Label Dose-Titration Cohort:
- To assess the tolerability and safety of a dazucorilant dose-titration regimen in patients with ALS

Secondary objectives 5

1. Part 1: To assess the effect of dazucorilant on muscle strength
2. Part 1: To assess the effect of dazucorilant on scales assessing Quality of Life and function including Slow Vital Capacity (SVC)
3. Part 1: To assess the effect of dazucorilant on time to event for patients experiencing: − Full time or nearly full-time respiratory support − Death − Death or full-time or nearly full-time respiratory support
4. Part 1: To assess the effect of dazucorilant on Combined Assessment of Function and Survival (CAFS)
5. Part 1: To assess the PK of dazucorilant in patients with ALS

Conditions and MedDRA coding

Amyotrophic Lateral Sclerosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Male and female patients ≥18 years of age with ALS as defined by Gold Coast criteria
2. Patients with sporadic or familial ALS. In Part 1 patients must have a risk of ALS progression characterized by an ENCALS risk profile score ≥ -6 and ≤ -3. In Part 2 patients must have a risk of ALS progression characterized by an ENCALS risk profile score ≥ -7 and ≤ -3.
3. Regulatory-authority-approved therapies for the treatment of ALS are permitted. If taking riluzole, edaravone, and/or sodium phenylbutyrate and taurursodiol, must have been on a stable dose of riluzole for ≥30 days, edaravone for ≥60 days and/or sodium phenylbutyrate and taurursodiol maintenance dosage ≥30 days prior to Screening. Sodium phenylbutyrate and taurursodiol are not permitted for patients enrolled in Part 2 of the study.
4. Medically able to undergo the study procedures and to adhere to the visit schedule at the time of study entry, as determined by the Investigator.
5. Able to understand the purpose and risks of the study; willing and able to adhere to scheduled visits, treatment plans, laboratory tests, and other study evaluations and procedures.
6. Provide written informed consent for participation in the study. If the patient is willing to sign the ICF but cannot physically sign it, an impartial witness must sign the ICF. Patients who are unable to come to the site in-person following informed consent for initial study participation may subsequently be consented remotely if allowed by local regulations/IRBs.
7. Male patients and female patients of childbearing potential must agree to use a protocol-specified method of contraception from screening and during the study until 28 days after last dose of study drug
8. Part 2 only: Patients with a pathogenic mutation in superoxide dismutase 1 (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.
9. 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 27

1. History of a clinically significant non-ALS neurologic disorder, including, but not limited to, muscular dystrophy, spinal stenosis, peripheral neuropathy, inherited neuropathies, Alzheimer’s disease, cervical spondylosis, Parkinson’s disease, Lewy body dementia, vascular dementia, Huntington’s disease, epilepsy, stroke, multiple sclerosis, multifocal motor neuropathy, diabetic neuropathy, brain tumor, or brain infection/abscess.
2. Inability to swallow capsules.
3. Blood platelet count <150,000/mm3.
4. Renal impairment indicated by eGFR ≤30 mL/min/1.73m2. Part 2 only: Patients with a recent history of acute kidney injury should have returned to their baseline renal function prior to enrollment.
5. Human immunodeficiency virus (HIV) or current chronic/active infection with hepatitis C virus or hepatitis B virus including patients with chronic or active hepatitis B as diagnosed by serologic tests. 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.
6. Women who are pregnant, planning to become pregnant, or are breastfeeding. Women of childbearing potential who are unwilling or unable to use a highly effective method of contraception from screening through the duration of treatment and up to 28 days after last dose of study drug.
7. Known liver impairment (Child-Pugh Class A, B, or C).
8. History of Class III/IV heart failure (per New York Heart Association).
9. At the time of Screening, any use of non-invasive ventilation (NIV), e.g., continuous positive airway pressure [CPAP], noninvasive bi-level positive airway pressure [NPPV] or noninvasive volume ventilation [NVV] for any portion of the day, or mechanical ventilation via tracheostomy, or on any form of oxygen supplementation.
10. Any form of cancer within the 5 years before first dose in this study (with the exception of basal cell and/or squamous cell cancer of the skin that has been treated completely and is without evidence of local recurrence or metastasis).
11. History of any other clinically significant cardiovascular, renal, hepatic, endocrine, metabolic, respiratory, gastrointestinal (GI), bleeding, autoimmune, neurological, psychiatric disorder, or unstable medical condition (other than ALS), as judged by the Investigator.
12. History and/or symptoms of adrenal insufficiency.
13. Abnormal liver function defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >3 × upper limit of normal (ULN).
14. QTcF interval based on the mean of 2 ECGs of >450 ms, for men and >470 ms for women.
15. History of additional risk factors for torsades de pointes (e.g., heart failure, hypokalemia, family history of long-QT syndrome).
16. Positive nasopharyngeal PCR test for SARS-CoV-2 on Day -1 or within 8 weeks prior to Screening.
17. Ongoing use of any strong CYP3A4 inhibitor/inducer, or any medication with a narrow therapeutic index that is predominantly metabolized by CYP2C8 or is a substrate of breast cancer resistance protein (BCRP) or P-glycoprotein 1 (P gp) that cannot be adequately dose adjusted.
18. Taking, or have taken, any strong CYP3A inducer within 30 days (or 5 half-lives if longer) before Screening, or any strong CYP3A inhibitor within 14 days before Screening.
19. Current or anticipated need, in the opinion of the Investigator, of a diaphragm pacing system (DPS) during the study period.
20. Received any live or attenuated vaccine within 30 days, before the first dose of study drug.
21. Currently using glucocorticoids or have a history of regular systemic glucocorticoid use at any dose within the last 12 months or 3 months for inhaled products before first dose of study drug. (Patients who have stopped glucocorticoid use should have an alternative option if their condition deteriorates during the study.)
22. Participation in a clinical trial for ALS involving small molecules within 30 days of the Screening, or treatment with another investigational drug (including through compassionate use programs), biological agent, or device within 30 days or 5 half-lives of study agent, whichever is longer. No prior treatment with small interfering RNA, stem cell therapy, or gene therapy is allowed at any time in the patient’s history.
23. Unstable or poorly controlled comorbid disease process of any organ system currently requiring active treatment or likely to require treatment adjustment during the study.
24. Previous exposure or treatment with glucocorticoid receptor modulators or antagonists.
25. History of hypersensitivity or severe reaction to the study drug’s excipients.
26. In the Investigator’s opinion, should not participate in the study or may not be capable of providing informed consent or following the study schedule. This includes, but is not limited to, presence of unstable psychiatric disease, cognitive impairment, dementia, or substance abuse within 2 years prior to Screening.
27. Is a family member of one of the Sponsor’s employees, the Investigator, or the site staff working directly on the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Part 1: Change from Baseline to Week 24 in the ALS Functional Rating Scale-Revised (ALSFRS-R) total score
2. Part 1: Incidence of AEs, SAEs, treatment-related AEs, AEs by severity, and death due to AEs
3. Part 2: Incidence of treatment-emergent AEs and SAEs
4. Part 2: Incidence of treatment-emergent AEs leading to dose interruptions, dose reductions, and/or discontinuations of study drug

Secondary endpoints 7

1. Part 1: Change from Baseline to Week 24 in muscle strength (assessed using hand-held dynamometer)
2. Part 1: Change from Baseline to Week 24 in: − Percent Slow Vital Capacity − EQ-5D-5L
3. Part 1: Time to death
4. Part 1: Time to respiratory support >22 hours per day for 7 days
5. Part 1: Time to death or time to respiratory support >22 hours per day for 7 days
6. Part 1: Combined Assessment of Function and Survival (CAFS)
7. Part 1: Plasma samples for pharmacokinetic (PK) analysis will be obtained in a dedicated PK substudy in a subset (~20%) of patients at the Week 3 visit. The dazucorilant AUC and Cmax will be reported.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Corcept Therapeutics Inc.

Sponsor organisation

Corcept Therapeutics Inc.

Address

101 Redwood Shores Parkway

City

Redwood City

Postcode

94065-1176

Country

United States

Scientific contact point

Organisation

Corcept Therapeutics Inc.

Contact name

Corcept Therapeutics Incorporated

Public contact point

Organisation

Corcept Therapeutics Inc.

Contact name

Corcept Therapeutics Incorporated

Third parties 11

Sponsor responsibilities

Article 77 compliance

Corcept Therapeutics Inc.

Contact point sponsor

Corcept Therapeutics Inc.

Article 77 implementation

Corcept Therapeutics Inc.

Locations

7 EU/EEA countries · 28 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications