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

Cushing Syndrome Clinical Trial

— GRACE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03697109
• Other study ID #: CORT125134-455
• Status: Completed
• Phase: Phase 3
• Start date: November 15, 2018
• Est. completion date: April 15, 2024

Study information

• Verified date: June 2024
• Source: Corcept Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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 and/or uncontrolled hypertension

Description:

This Phase 3 study involves two phases, an open-label (OL) phase and a randomized-withdrawal (RW) phase. Patients will dose-escalate in 100 mg increments to a target dose of 400 mg orally once daily during the open-label phase. Patients will remain on open-label treatment until week 22 at which time they will be evaluated for the randomized-withdrawal phase based on pre-defined 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 randomization will end treatment and may be eligible to roll over into an extension safety study. Patients who complete the randomized-withdrawal phase of the study may also be eligible to roll over into an extension study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 152
• Est. completion date: April 15, 2024
• Est. primary completion date: April 8, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Has a confirmed diagnosis of endogenous Cushing syndrome

• Meets at least one of the following criteria:

• Has Type 2 diabetes mellitus

• Has impaired glucose tolerance

• Has hypertension

Exclusion Criteria:

• Has non-endogenous source of hypercortisolemia

• Has uncontrolled, clinically significant hypothyroidism or hyperthyroidism

• Has poorly controlled hypertension

• Has poorly controlled diabetes mellitus

• Has severe renal insufficiency

Related Conditions & MeSH terms

• Cushing Syndrome
• Syndrome

Intervention

Drug:
• Relacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.

Other:
• Placebo
Placebo matched to study drug

Locations

Country	Name	City	State
Austria	Site 60	Graz
Austria	Site 47	Vienna
Bulgaria	Site 27	Sofia
Canada	Site 70	Halifax	Nova Scotia
Germany	Site 54	München
Germany	Site 49	Würzburg
Israel	Site 29	Kfar Saba
Israel	Site 28	Petach Tikva
Israel	Site 69	Tel Aviv
Italy	Site 43	Ancona
Italy	Site 15	Messina
Italy	Site 26	Milano
Italy	Site 12	Napoli
Italy	Site 38	Orbassano
Italy	Site 16	Roma
Italy	Site 40	Roma
Netherlands	Site 34	Rotterdam
Poland	Site 59	Kraków
Poland	Site 33	Lublin
Romania	Site 63	Bucharest
Romania	Site 64	Bucharest
Romania	Site 66	Bucharest
Spain	Site 75	Alicante
Spain	Site 74	Barcelona
Spain	Site 25	Girona
Spain	Site 24	Madrid
Spain	Site 22	Málaga
Spain	Site 23	Sevilla
United States	Site 8	Albany	New York
United States	Site 20	Ann Arbor	Michigan
United States	Site 14	Atlanta	Georgia
United States	Site 45	Baltimore	Maryland
United States	Site 17	Columbus	Ohio
United States	Site 51	Dallas	Texas
United States	Site 3	El Paso	Texas
United States	Site 65	Houston	Texas
United States	Site 7	Indianapolis	Indiana
United States	Site 4	Jackson	Mississippi
United States	Site 36	Los Angeles	California
United States	Site 2	Metairie	Louisiana
United States	Site 10	Miami	Florida
United States	Site 57	New York	New York
United States	Site 11	Oklahoma City	Oklahoma
United States	Site 53	Omaha	Nebraska
United States	Site 62	Philadelphia	Pennsylvania
United States	Site 21	Phoenix	Arizona
United States	Site 71	Pittsburgh	Pennsylvania
United States	Site 68	Torrance	California

Sponsors (1)

Lead Sponsor	Collaborator
Corcept Therapeutics

Countries where clinical trial is conducted

United States,  Austria,  Bulgaria,  Canada,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Romania,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	In patients with hypertension, the proportion of patients with a loss of response with respect to hypertension from visit OL22 to RW12	Based on 24hour ABPM defined as 1) an increase in systolic and/or diastolic blood pressure of at least 5 mmHg or 2) any increase or modification in antihypertensive medication from Week OL22 to Week RW12/Early Termination as compared between relacorilant and placebo	Week OL22 to Week RW12
Primary	In all patients, assessment of safety based on treatment-emergent adverse events (TEAEs) as graded by CTCAE v5.0.		Screening through Post Treatment Follow-up (up to 48 weeks)
Secondary	In patients with diabetes mellitus/impaired glucose tolerance (DM/IGT), the mean change in area under the curve for glucose from Week OL22 to Week RW12 as compared between relacorilant and placebo		Week Open label 22 (OL22) to Week Randomized withdraw 12 (RW12)
Secondary	In patients with DM (HbA1c at Baseline >6.5%), the mean change from Visit OL22 to RW12 in HbA1c as compared between relacorilant and placebo.		Open Label week 22 (OL22) to Randomized Withdraw week 12 (RW12)
Secondary	In patients with IGT at Baseline, the mean change from Visit OL22 to RW12 in the 2 hour glucose value of the oGTT		Week OL22 to week RW12
Secondary	In patients with hypertension the mean change in SBP or DBP as compared between relacorilant and placebo		Week OL22 to week RW12
Secondary	The mean change in body weight, body fat measured with DXA scan and Cushing Quality-of-Life (QoL) score as compared between relacorilant and placebo	The Cushing Quality of Life (QoL) patient questionnaire, which evaluates the health-related QoL in patients with Cushing syndrome (Webb et al. 2008), will be administered to all patients. It comprises 12 questions, each with 5 possible answers. The total score ranges from 12-60. 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. Lower values reflect lower quality of life.	Week OL22 to week RW12
Secondary	For patients in either subgroup (DM/IGT or hypertension) the proportion of patients with any increase or modification in diabetes or antihypertensive medication as compared between relacorilant and placebo		Week OL22 to week RW12
Secondary	Proportion of patients who worsened, as assessed by the Global Clinical Response, from Week OL22 to Week RW12/ET as compared between relacorilant and placebo	Global Clinical Response will be scored in 7 categories: glucose, blood pressure, body composition, clinical appearance, strength, psychiatric health/ cognitive function, Cushing QoL score.; An independent Data Review Board (DRB) will review the 7 categories of clinical parameters above to evaluate whether a patient's signs and symptoms of Cushing syndrome have changed and will rate each patient's overall response based on the totality of signs and symptoms as +1 (improved), 0 (unchanged), or -1 (worsened) at every visit after Baseline. Each patient's final score will be the median of the 3 ratings	Week OL22 to Week RW12
Secondary	Mean change in QoL, body fat composition as determined by DXA, Beck Depression inventory-II (BDI-II) and body weight from Baseline to visit OL22 or end of treatment (ET)		Baseline to week OL22 or End of Treatment (ET)
Secondary	In patients with IGT, the mean change in 2-hour oGTT glucose from Baseline to Visit OL22/ET		Baseline to week OL22 or ET
Secondary	In patients with DM (HbA1c =6.5% at Baseline), the mean change in HbA1c from Baseline to Visit OL22/ET		Baseline to week OL22 or ET
Secondary	In patients with uncontrolled hypertension the mean change in SBP or DBP from Baseline to visit OL22/ET	Blood pressure will be measured by 24 hour ABPM readings	Baseline to week OL22 or ET