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NCT03697109: GRACE

A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome

Completed Phase 3 Results posted Last updated 16 July 2025
What this trial tests

Phase 3 trial testing Relacorilant in Cushing Syndrome in 152 participants. Completed in 15 April 2024.

Timeline
15 November 2018
Primary endpoint
8 April 2024
15 April 2024

Quick facts

Lead sponsorCorcept Therapeutics
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingtriple
Primary purposetreatment
Enrollment152
Start date15 November 2018
Primary completion8 April 2024
Estimated completion15 April 2024
Sites64 locations across Italy, Netherlands, Austria, Germany, Israel, Poland, Romania, Canada

Drugs / interventions tested

Conditions studied

Sponsor

Corcept Therapeutics — full company profile →

Who can join

Adults 18 to 80, any sex, with Cushing Syndrome. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase. Primary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

Loss of response with respect to HTN was measured using 6 criteria: 1) an increase in SBP of at least 5 mm Hg, 2) an increase in DBP of at least 5 mm Hg, 3) an increase in SBP and/or DBP of at least 5 mm Hg, 4) use of HTN rescue medication, 5) treatment discontinuation, and 6) missing 24-hour ambulatory blood pressure monitoring (ABPM) measurement at the end of the RW Phase. Blood pressure was measured using ABPM. Use of rescue medication was defined as any increase, modification, or addition of antihypertensive medication due to worsening HTN. Treatment discontinuation reports the number of p

SBP
GroupValue95% CI
Relacorilant (RW Phase)3
Placebo (RW Phase)1
DBP
GroupValue95% CI
Relacorilant (RW Phase)1
Placebo (RW Phase)1
SBP and/or DBP
GroupValue95% CI
Relacorilant (RW Phase)3
Placebo (RW Phase)4
Use of rescue medication
GroupValue95% CI
Relacorilant (RW Phase)0
Placebo (RW Phase)7
Treatment discontinuation
GroupValue95% CI
Relacorilant (RW Phase)2
Placebo (RW Phase)3
Missing ABPM at end of RW Phase
GroupValue95% CI
Relacorilant (RW Phase)2
Placebo (RW Phase)3
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0. Primary · OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
GroupValue95% CI
Relacorilant (OL Phase)147
Relacorilant (RW Phase)23
Placebo (RW Phase)27
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase Secondary · Before and at time intervals up to 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
GroupValue95% CI
Relacorilant (RW Phase)1.91-1.138 – 4.966
Placebo (RW Phase)4.812.096 – 7.529
Change in Hemoglobin HbA1c During the RW Phase Secondary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
GroupValue95% CI
Relacorilant (RW Phase)0.06-0.270 – 0.383
Placebo (RW Phase)0.28-0.022 – 0.578
Change in 2-hour Plasma Glucose During the RW Phase Secondary · Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT).

GroupValue95% CI
Relacorilant (RW Phase)0.52-1.06 – 2.09
Placebo (RW Phase)2.961.55 – 4.37
Change in SBP and DBP During the RW Phase Secondary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

Blood pressure was measured by 24-hour ABPM.

SBP
GroupValue95% CI
Relacorilant (RW Phase)3.950.470 – 7.424
Placebo (RW Phase)10.436.538 – 14.329
DBP
GroupValue95% CI
Relacorilant (RW Phase)2.86-0.199 – 5.928
Placebo (RW Phase)6.533.224 – 9.832
Change in Body Weight During the RW Phase Secondary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
GroupValue95% CI
Relacorilant (RW Phase)-1.21-2.685 – 0.269
Placebo (RW Phase)0.54-0.851 – 1.939
Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase Secondary · Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
GroupValue95% CI
Relacorilant (RW Phase)1
Placebo (RW Phase)0
Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase Secondary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.

GroupValue95% CI
Relacorilant (RW Phase)0.59-4.28 – 5.46
Placebo (RW Phase)-0.58-5.14 – 3.98
Percent Change in Tissue Fat Mass During the RW Phase Secondary · Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)

Tissue fat mass was measured by dual energy X-ray absorptiometry (DXA) scan. Reported are change in in absolute tissue fat mass and change in percent tissue fat mass.

Absolute Tissue Fat Mass
GroupValue95% CI
Relacorilant (RW Phase)-0.64-1.684 – 0.400
Placebo (RW Phase)1.670.776 – 2.573
Percent Tissue Fat Mass
GroupValue95% CI
Relacorilant (RW Phase)-0.14-1.031 – 0.759
Placebo (RW Phase)1.660.887 – 2.437
Change in Percent Tissue Fat Mass During the OL Phase Secondary · Baseline and Week 22 (end of OL Phase)

Tissue fat mass was measured by DXA scan.

Baseline Percent Tissue Fat Mass
GroupValue95% CI
Relacorilant (OL Phase)46.4± 8.39
Change from Baseline in Percent Tissue Fat Mass at Week 22
GroupValue95% CI
Relacorilant (OL Phase)-1.8± 2.73
Change in Cushing QoL Normalized Total Score During the OL Phase Secondary · Baseline and Week 22 (end of OL Phase)

The Cushing QoL patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome, comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60, with a higher score indicating improvement in QoL. The Cushing QoL instrument addresses known problem areas associated with Cushing syndrome including trouble sleeping, wound healing/bruising, irritability/mood swings/anger, self-confidence, physical changes, ability to participate in activities, interactions with friends and family, memory issues, and future health concerns.

Baseline Cushing QoL Score
GroupValue95% CI
Relacorilant (OL Phase)41.9± 19.78
Change from Baseline in Cushing QoL Score
GroupValue95% CI
Relacorilant (OL Phase)7.4± 14.63

Adverse events — posted to ClinicalTrials.gov

Time frame: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Relacorilant (OL Phase)
Serious: 29/152 (19%)
Deaths: 2/152
Relacorilant (RW Phase)
Serious: 5/30 (17%)
Deaths: 0/30
Placebo (RW Phase)
Serious: 1/32 (3%)
Deaths: 0/32

Serious adverse events (50 terms)

ReactionSystemRelacorilant (OL Phase)Relacorilant (RW Phase)Placebo (RW Phase)
HypotensionVascular disorders
HyperkalaemiaMetabolism and nutrition disorders
Atrial fibrillationCardiac disorders
Acute kidney injuryRenal and urinary disorders
Chronic obstructive pulmonary diseaseRespiratory, thoracic and mediastinal disorders
Bone abscessInfections and infestations
COVID-19Infections and infestations
COVID-19 pneumoniaInfections and infestations
Cavernous sinus thrombosisInfections and infestations
DiverticulitisInfections and infestations
EpididyitisInfections and infestations
OsteomyelitisInfections and infestations
PneumoniaInfections and infestations
Pseudomonal sepsisInfections and infestations
Rectal abscessInfections and infestations
SepsisInfections and infestations
Sinusitis fungalInfections and infestations
Staphylococcal osteomyelitisInfections and infestations
Urinary tract infectionInfections and infestations
Wound abscessInfections and infestations
HyponatraemiaMetabolism and nutrition disorders
HypoglycaemiaMetabolism and nutrition disorders
HypokalaemiaMetabolism and nutrition disorders
Cardiac failure chronicCardiac disorders
Coronary artery diseaseCardiac disorders
Other adverse events (43 terms — click to expand)

ReactionSystemRelacorilant (OL Phase)Relacorilant (RW Phase)Placebo (RW Phase)
NauseaGastrointestinal disorders
Oedema peripheralGeneral disorders
Pain in extremityMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
FatigueGeneral disorders
HeadacheNervous system disorders
ArthralgiaMusculoskeletal and connective tissue disorders
DiarrhoeaGastrointestinal disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders
Abdominal pain upperGastrointestinal disorders
ConstipationGastrointestinal disorders
DizzinessNervous system disorders
MyalgiaMusculoskeletal and connective tissue disorders
ParaesthesiaNervous system disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Muscular weaknessMusculoskeletal and connective tissue disorders
Abdominal painGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Peripheral swellingGeneral disorders
PainGeneral disorders
Neuropathy peripheralNervous system disorders
AcneSkin and subcutaneous tissue disorders
InsomniaPsychiatric disorders
Urinary tract infectionInfections and infestations
HypotensionVascular disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
Dry skinSkin and subcutaneous tissue disorders
RashSkin and subcutaneous tissue disorders
COVID-19Infections and infestations
DyspepsiaGastrointestinal disorders
PruritusSkin and subcutaneous tissue disorders
HypokalaemiaMetabolism and nutrition disorders
BursitisMusculoskeletal and connective tissue disorders
NasopharyngitisInfections and infestations
PyrexiaGeneral disorders
HypoaesthesiaNervous system disorders
FolliculitisInfections and infestations
HypertensionVascular disorders
IrritabilityPsychiatric disorders

Most-reported serious reactions: Hypotension, Hyperkalaemia, Atrial fibrillation, Acute kidney injury, Chronic obstructive pulmonary disease, Bone abscess, COVID-19, COVID-19 pneumonia.

Data from ClinicalTrials.gov NCT03697109 adverse events section.

Sponsor's own description

This is a Phase 3, double-blind, placebo-controlled, randomized-withdrawal study to assess the efficacy, safety and pharmacokinetics (PK) of relacorilant in patients with endogenous Cushing syndrome and concurrent type 2 diabetes mellitus/impaired glucose tolerance (DM/IGT) and/or uncontrolled hypertension (HTN).

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Medical Treatment of Cushing's Disease: An Overview of the Current and Recent Clinical Trials.
    Pivonello R, Ferrigno R, De Martino MC, Simeoli C, et al · · 2020 · cited 84× · PMID 33363514 · DOI 10.3389/fendo.2020.00648
  2. Relacorilant, a Selective Glucocorticoid Receptor Modulator, Induces Clinical Improvements in Patients With Cushing Syndrome: Results From A Prospective, Open-Label Phase 2 Study.
    Pivonello R, Bancos I, Feelders RA, Kargi AY, et al · · 2021 · cited 51× · PMID 34335465 · DOI 10.3389/fendo.2021.662865
  3. Overcoming Taxane Resistance: Preclinical and Phase 1 Studies of Relacorilant, a Selective Glucocorticoid Receptor Modulator, with Nab-Paclitaxel in Solid Tumors.
    Munster PN, Greenstein AE, Fleming GF, Borazanci E, et al · · 2022 · cited 25× · PMID 35583817 · DOI 10.1158/1078-0432.ccr-21-4363
  4. Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells.
    Greenstein AE, Hunt HJ. · · 2021 · cited 24× · PMID 34194622 · DOI 10.18632/oncotarget.27989
  5. Individualized medical treatment options in Cushing disease.
    Gilis-Januszewska A, Bogusławska A, Rzepka E, Ziaja W, et al · · 2022 · cited 23× · PMID 36531477 · DOI 10.3389/fendo.2022.1060884
  6. Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.
    Jin P, Duan X, Huang Z, Dong Y, et al · · 2025 · cited 21× · PMID 40717128 · DOI 10.1038/s41392-025-02270-3
  7. Genetically engineered human pituitary corticotroph tumor organoids exhibit divergent responses to glucocorticoid receptor modulators.
    Mallick S, Chakrabarti J, Eschbacher J, Moraitis AG, et al · · 2023 · cited 15× · PMID 36640905 · DOI 10.1016/j.trsl.2023.01.002
  8. Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant.
    Pivonello R, Munster PN, Terzolo M, Ferrigno R, et al · · 2021 · cited 15× · PMID 35058882 · DOI 10.3389/fendo.2021.793262

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Other trials of Relacorilant

Trials testing the same drug.

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Currently open trials in the same condition.

Other Corcept Therapeutics trials

Trials by the same sponsor.

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Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing