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

Glucocorticoid Receptor Antagonism in the Treatment of Cushing Syndrome (GRACE): A Phase 3, Double-Blind, Placebo-Controlled, Randomized-Withdrawal Study of the Efficacy and Safety of Relacorilant

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).

Study Overview

• Status: Completed
• Conditions: Cushing Syndrome
• Intervention / Treatment: Drug: Relacorilant; Other: Placebo

Detailed Description

The primary outcome is the assessment of efficacy of relacorilant treatment based on sustained blood pressure control during the Randomized-withdrawal (RW) Phase, wherein patients who had achieved the blood pressure response criteria during the Open-label (OL) Phase are randomized to receive either relacorilant or placebo for 12 weeks.

Patients in the OL Phase will dose-escalate in 100 mg increments to a maximum dose of 400 mg orally once daily. Patients will remain on OL treatment until Week 22 at which time they will be evaluated for the RW Phase based on predefined hyperglycemia and hypertension response criteria. Eligible patients will then be randomized to receive either relacorilant or placebo at a 1:1 ratio for 12 weeks. Patients who do not meet the criteria for the RW Phase will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the RW Phase of the study may also be eligible to roll over into an extension study.

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • Site 47
• Bulgaria
  • Sofia, Bulgaria, 1431
    • Site 27
• Canada
  • Montréal, Canada, H2X 0A9
    • Site 58
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H-2Y9
      • Site 70
• Germany
  • München, Germany, 80336
    • Site 54
  • Würzburg, Germany, 97080
    • Site 49
• Israel
  • Jerusalem, Israel, 911120
    • Site 30
  • Kfar Saba, Israel, 4428164
    • Site 29
  • Petach Tikva, Israel, 4941480
    • Site 28
  • Tel Aviv, Israel
    • Site 69
• Italy
  • Ancona, Italy, 60030
    • Site 43
  • Messina, Italy, 98125
    • Site 15
  • Milano, Italy, 20149
    • Site 26
  • Napoli, Italy, 80131
    • Site 12
  • Orbassano, Italy, 10043
    • Site 38
  • Padova, Italy, 35128
    • Site 67
  • Roma, Italy, 00161
    • Site 40
  • Roma, Italy, 00189
    • Site 16
• Netherlands
  • Rotterdam, Netherlands, 3015 AA
    • Site 34
• Poland
  • Bialystok, Poland
    • Site 77
  • Chrzanów, Poland, 32-500
    • Site 37
  • Kraków, Poland, 31- 501
    • Site 59
  • Lublin, Poland, 20-412
    • Site 33
• Romania
  • Bucharest, Romania, 010825
    • Site 66
  • Bucharest, Romania, 011863
    • Site 63
  • Bucharest, Romania, 011863
    • Site 64
  • Iaşi, Romania, 700106
    • Site 73
• Spain
  • Alicante, Spain, 03010
    • Site 75
  • Girona, Spain, 17007
    • Site 25
  • Madrid, Spain, 28007
    • Site 24
  • Málaga, Spain, 29006
    • Site 22
  • Sevilla, Spain, 41013
    • Site 23
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Site 21
  • California
    • Los Angeles, California, United States, 90095
      • Site 36
    • Torrance, California, United States, 90502
      • Site 68
  • Florida
    • Miami, Florida, United States, 33136
      • Site 10
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Site 14
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Site 41
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Site 7
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Site 2
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Site 45
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Site 46
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Site 20
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Site 4
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Site 13
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Site 53
  • Nevada
    • Reno, Nevada, United States, 89511
      • Site 72
  • New York
    • Albany, New York, United States, 12203
      • Site 8
    • Jamaica, New York, United States, 11432
      • Site 6
    • New York, New York, United States, 10021
      • Site 57
    • New York, New York, United States, 10029
      • Site 35
    • New York, New York, United States, 10065
      • Site 39
  • North Carolina
    • Wilmington, North Carolina, United States, 28401
      • Site 1
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Site 17
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Site 11
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Site 62
    • Pittsburgh, Pennsylvania, United States, 15213
      • Site 71
    • Pittsburgh, Pennsylvania, United States, 15212
      • Site 19
  • South Carolina
    • Summerville, South Carolina, United States, 29485
      • Site 5
  • Texas
    • Dallas, Texas, United States, 75390
      • Site 51
    • El Paso, Texas, United States, 79935
      • Site 3
    • Houston, Texas, United States, 77079
      • Site 65
    • Shavano Park, Texas, United States, 78231
      • Site 56
  • Washington
    • Everett, Washington, United States, 98201
      • Site 31

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has a confirmed diagnosis of endogenous Cushing syndrome

• Meets at least 1 of the following criteria:

  • Has Type 2 diabetes mellitus
  • Has impaired glucose tolerance
  • Has hypertension.

Exclusion Criteria:

• Has non-endogenous source of hypercortisolism
• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism
• Has poorly controlled hypertension
• Has poorly controlled diabetes mellitus
• Has severe renal insufficiency.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Relacorilant (OL Phase); Patients will receive relacorilant increased sequentially from 100 mg once daily to a maximum dose of 400 mg once daily.	Drug: Relacorilant; Relacorilant is supplied as 100 mg capsules for oral dosing.; Other Names: CORT125134
Experimental: Relacorilant (RW Phase); Patients who meet any of the response criteria will advance to the RW Phase of the study and receive the same dose of relacorilant as the last dose administered in the OL Phase.	Drug: Relacorilant; Relacorilant is supplied as 100 mg capsules for oral dosing.; Other Names: CORT125134
Placebo Comparator: Placebo (RW Phase); Patients who meet any of the response criteria will advance to the RW Phase of the study and receive placebo matched to study drug.	Other: Placebo; Placebo matched to study drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Patients With Loss of Response With Respect to Hypertension During the 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 patients who discontinued study treatment in the RW Phase for any reason.	Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.		OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase		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)
Change in Hemoglobin HbA1c During the RW Phase		Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in 2-hour Plasma Glucose During the RW Phase	Plasma glucose was measured using the 2-hour Oral Glucose Tolerance Test (oGTT).	Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in SBP and DBP During the RW Phase	Blood pressure was measured by 24-hour ABPM.	Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Change in Body Weight During the RW Phase		Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase		Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cushing Quality of Life (QoL) Normalized Total Score During the 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.	Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Percent Change in Tissue Fat Mass During the 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.	Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase	The Global Clinical Response assessment measures the patient's signs and symptoms of endogenous hypercortisolism in 7 clinical categories: 1) glucose parameters, 2) blood pressure parameters, 3) body composition parameters, 4) clinical appearance, 5) strength parameters, 6) psychiatric health/cognitive function parameters, and 7) quality of life using the Cushing QoL score. The overall response based on the totality of signs and symptoms is rated as +1 for improved, 0 for unchanged, and -1 for worsened. Each patient's final score is the median of ratings given by 3 members of the Data Review Board.	Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
Change in Percent Tissue Fat Mass During the OL Phase	Tissue fat mass was measured by DXA scan.	Baseline and Week 22 (end of OL Phase)
Change in Cushing QoL Normalized Total Score During the 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 and Week 22 (end of OL Phase)
Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase	The BDI-II is a 21-question self-report inventory that measures depression. Each answer is scored with values of 0 to 3. The total score ranges from 0 to 63. Scores of 0 to 13 indicate minimal depression, 14 to 19; mild depression; 20 to 28; moderate depression; 29 to 63; severe depression.	Baseline and Week 22 (end of OL Phase)
Mean Change From Baseline in Body Weight During the OL Phase		Baseline and Week 22 (end of OL Phase)
Change in 2-hour Plasma Glucose During the OL Phase	Plasma glucose was measured using the 2-hour oGTT.	Baseline and Week 22 (end of OL Phase)
Change in Hemoglobin HbA1c During the OL Phase		Baseline and Week 22 (end of OL Phase)
Change in SBP and DBP During the OL Phase	Blood pressure was measured by 24-hour ABPM.	Baseline and Week 22 (end of OL Phase)

Collaborators and Investigators

• Sponsor: Corcept Therapeutics
• Investigators: Study Director: Andreas Moraitis, MD, Corcept Therapeutics

Publications and helpful links

General Publications

• Pivonello R, Munster PN, Terzolo M, Ferrigno R, Simeoli C, Puglisi S, Bali U, Moraitis AG. Glucocorticoid Receptor Antagonism Upregulates Somatostatin Receptor Subtype 2 Expression in ACTH-Producing Neuroendocrine Tumors: New Insight Based on the Selective Glucocorticoid Receptor Modulator Relacorilant. Front Endocrinol (Lausanne). 2022 Jan 4;12:793262. doi: 10.3389/fendo.2021.793262. eCollection 2021.

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2018
• Primary Completion (Actual): April 8, 2024
• Study Completion (Actual): April 15, 2024

Study Registration Dates

• First Submitted: September 27, 2018
• First Submitted That Met QC Criteria: October 3, 2018
• First Posted (Actual): October 5, 2018

Study Record Updates

• Last Update Posted (Actual): July 16, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Hypertension; Type 2 Diabetes; Cortisol; Cushing syndrome; Cushing disease; Hypercortisolemia; Cushingoid; Impaired Glucose Intolerance; Adrenocorticotropic hormone; Primary Pigmented Nodular Adrenal Disease; Moon Facies; Dorsocervical Fat Pad; Adrenal Adenoma; Adrenal Autonomy; Cushing
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Disease; Adrenal Gland Diseases; Adrenocortical Hyperfunction; Syndrome; Cushing Syndrome
• Other Study ID Numbers: CORT125134-455

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No