Extension of a clinical trial to assess the safety of a study drug called "CORT125134" in the treatment of Cushing Syndrome

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

Phenomena and Processes [G] - Physiological processes [G07]

Trial duration

28 May 2020 → ongoing

Decision date (initial)

2024-10-20

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2024-514079-17-00

EudraCT number

2018-001616-30

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Dose response, Pharmacogenetic, Pharmacodynamic, Efficacy, Safety

To assess the long-term safety of relacorilant in the treatment of the signs and symptoms of endogenous Cushing syndrome

Conditions and MedDRA coding

Endogenous Cushing Syndrome

Regulatory references

Plan to share IPD

Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Have completed a Corcept-sponsored study of relacorilant in endogenous Cushing syndrome.
2. According to Investigator's opinion will benefit from treatment with relacorilant.
3. Provide written informed consent.
4. If a female of childbearing potential, patients must be willing to use a highly effective method of contraception from 30 days before study entry until 28 days after the last dose of study drug. Male patients with a female partner must agree to 2 forms of contraception, one of which must be a double-barrier method, from study entry until 28 days after the last dose of study drug. Highly effective methods of contraception are detailed in the protocol.
5. Are willing to continue to refrain from using drugs that inhibit steroid biosynthesis by the adrenal cortex or ACTH secretion by a pituitary or extra pituitary ACTH secreting tumor.
6. Are able to return to the investigative site to complete the study evaluations outlined in the protocol.
7. For patients with Cushing syndrome due to an ACTH-secreting pituitary tumor, are able to obtain pituitary MRI imaging (up to 6 months before starting treatment in this study, or up to 6 weeks after start of treatment in this study) to assess changes in tumor size during dosing. A CT scan can be used instead in patients for whom MRI is contraindicated.
8. For patients entering the study >12 weeks after completing the last dose in the parent study, confirmation of hypercortisolism consistent with the criteria of the parent study is required.
9. For patients who received treatment for hypercortisolism after their last dose in the parent study, confirmation of hypercortisolism consistent with the criteria of the parent study is required.

Exclusion criteria 18

1. Have been prematurely discontinued from relacorilant study treatment in the parent study for any reason.
2. Are planning to start another Cushing syndrome drug after starting participation in this extension study.
3. Have an acute or unstable medical problem that could be aggravated by relacorilant treatment or has known active COVID-19 infection at Screening.
4. Are taking the following medications from the times specified below before the Study CORT125134-452 Day 1 visit and/or through the entire study period: • Medications used in the treatment of Cushing syndrome, with the exception of relacorilant, are prohibited: – Adrenostatic medications: metyrapone, osilodrostat, ketoconazole, fluconazole, aminoglutethimide, or etomidate 4 weeks before Day 1 through the end of this study – Neuromodulator drugs that act at the hypothalamic-pituitary level: serotonin antagonists (cyproheptadine, ketanserin, ritanserin), dopamine agonists (bromocriptine, cabergoline), gamma-aminobutyric acid agonists (sodium valproate), and somatostatin receptor ligands (octreotide long-acting release [LAR], pasireotide LAR, lanreotide) from 8 weeks before Day 1 through the end of this study. Use of short-acting somatostatin analogs (octreotide, pasireotide) from 4 weeks before Day 1 through the end of this study. • Patients who require inhaled glucocorticoid use and have no alternative option if their condition deteriorates during the study. • Mifepristone, from 4 weeks before Day 1. • Ongoing use of any strong CYP3A inducers during treatment with relacorilant. • Has used mitotane prior to Day 1. • Ongoing use of antidiabetic, antihypertensive, antidepressant, and/or lipid-lowering medications that are highly dependent on CYP3A for clearance and that cannot undergo dose modifications upon coadministration with strong CYP3A inhibitors.
5. Plans for prolonged regular use of systemic glucocorticoids from Day 1 through the end of the study.
6. Have received investigational treatment (drug, biological agent, or device) other than relacorilant within 4 weeks of study entry, or within 5 times the drug's half-life, whichever is longer.
7. Have a history of an allergic reaction or intolerance to relacorilant.
8. Have uncorrected clinically significant hypokalemia (potassium level of < 3 mEq/L) within 2 weeks before enrollment in this study (Day 1).
9. Have uncontrolled, clinically significant hypothyroidism or hyperthyroidism.
10. Have renal failure as defined by a serum creatinine of ≥2.2 mg/dL.
11. Have elevated total bilirubin >1.5 × the ULN or elevated alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3 × ULN.
12. Have a clinically significant ECG abnormality at baseline, which, in the opinion of the Investigator, will make the patient an unsuitable candidate for the study.
13. Have a confirmed baseline QT interval corrected using Fridericia's formula (QTcF) of >450 ms for males and >470 ms for females in the presence of a normal QRS interval (QRS <120 ms), a QTcF interval >500 ms with a wide QRS interval (≥120 ms),or a history of additional risk factors for torsades de pointes.
14. Has received stereotactic radiation therapy for a Cushing syndromerelated tumor within 24 months of Baseline or conventional pituitary radiation therapy within 36 months of Baseline.
15. Has undergone pituitary surgery <3 months prior to Screening.
16. Has plans for adrenalectomy or nodulectomy during the study, including follow-up.
17. Female who is pregnant or lactating.
18. Have an ongoing SAE that started in the parent study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 5

1. Incidence of treatment-emergent adverse events (TEAEs) (assessed monthly): TEAEs, serious TEAEs (SAEs), treatment-related TEAEs, TEAEs leading to early discontinuation of study treatment.
2. Changes from Baseline in clinical laboratory tests (hematology and chemistry panels).
3. Changes from Baseline in physical examinations and vital sign measurements.
4. Changes from Baseline in electrocardiograms (ECGs) (12-lead) (including QTcF interval, QRS complex, PR interval, and heart rate).
5. Changes from Baseline in pituitary tumors based on magnetic resonance imaging (MRI) scans in patients with Cushing disease.

Investigational products

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

Test 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 9

Locations

8 EU/EEA countries · 24 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 38 files

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

Application history

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