Clinical trial NCT03697109: A Study of the Efficacy and Safety of Relacorilant in Patients With Endogenous Cushing Syndrome
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cushing Syndrome
Keywords: Cushing syndrome
Cushing disease
Hypercortisolemia
Cushingoid
Type 2 Diabetes
Impaired Glucose Intolerance
Hypertension
Adrenocorticotropic hormone
Primary Pigmented Nodular Adrenal Disease
Moon Facies
Dorsocervical Fat Pad
Adrenal Adenoma
Adrenal Autonomy
Cortisol
Cushing
Lead sponsor: Corcept Therapeutics
Sponsor class: INDUSTRY
First posted: 2018-10-05
Enrollment: 152
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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 (DM/IGT) and/or uncontrolled hypertension (HTN).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Patients With Loss of Response With Respect to Hypertension During the RW Phase.
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Number of Patients With 1 or More Treatment-emergent Adverse Events (TEAEs) as Graded by CTCAE v5.0.
timeFrame: OL Phase: Up to 22 weeks; RW Phase: up to 18 weeks after completion of the OL Phase
Secondary outcomes:
measure: Change in Area Under the Concentration-time Curve of Blood Glucose (AUCglucose) During the RW Phase
timeFrame: 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)
measure: Change in Hemoglobin HbA1c During the RW Phase
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Change in 2-hour Plasma Glucose During the RW Phase
timeFrame: Before and 2 hours post glucose drink at Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Change in SBP and DBP During the RW Phase
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Change in Body Weight During the RW Phase
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Number of Patients With Any Increase or Modification in Diabetes Medication During the RW Phase
timeFrame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
Other outcomes:
measure: Change in Cushing Quality of Life (QoL) Normalized Total Score During the RW Phase
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Percent Change in Tissue Fat Mass During the RW Phase
timeFrame: Week 22 (end of OL Phase) and Week 36 (Week 12 of RW Phase)
measure: Number of Patients Who Worsened, as Assessed by the Global Clinical Response, During the RW Phase
timeFrame: Week 22 (end of OL Phase) and up to Week 36 (Week 12 of RW Phase)
measure: Change in Percent Tissue Fat Mass During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Change in Cushing QoL Normalized Total Score During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Change in Beck Depression Inventory-II (BDI-II) Score During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Mean Change From Baseline in Body Weight During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Change in 2-hour Plasma Glucose During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Change in Hemoglobin HbA1c During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
measure: Change in SBP and DBP During the OL Phase
timeFrame: Baseline and Week 22 (end of OL Phase)
Locations:
city: Phoenix
country: United States
facility: Site 21
state: Arizona
city: Los Angeles
country: United States
facility: Site 36
state: California
city: Torrance
country: United States
facility: Site 68
state: California
city: Miami
country: United States
facility: Site 10
state: Florida
city: Atlanta
country: United States
facility: Site 14
state: Georgia
city: Chicago
country: United States
facility: Site 41
state: Illinois
city: Indianapolis
country: United States
facility: Site 7
state: Indiana
city: Metairie
country: United States
facility: Site 2
state: Louisiana
city: Baltimore
country: United States
facility: Site 45
state: Maryland
city: Boston
country: United States
facility: Site 46
state: Massachusetts
city: Ann Arbor
country: United States
facility: Site 20
state: Michigan
city: Jackson
country: United States
facility: Site 4
state: Mississippi
city: Saint Louis
country: United States
facility: Site 13
state: Missouri
city: Omaha
country: United States
facility: Site 53
state: Nebraska
city: Reno
country: United States
facility: Site 72
state: Nevada
city: Albany
country: United States
facility: Site 8
state: New York
city: Jamaica
country: United States
facility: Site 6
state: New York
city: New York
country: United States
facility: Site 57
state: New York
city: New York
country: United States
facility: Site 35
state: New York
city: New York
country: United States
facility: Site 39
state: New York
city: Wilmington
country: United States
facility: Site 1
state: North Carolina
city: Columbus
country: United States
facility: Site 17
state: Ohio
city: Oklahoma City
country: United States
facility: Site 11
state: Oklahoma
city: Philadelphia
country: United States
facility: Site 62
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Site 19
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Site 71
state: Pennsylvania
city: Summerville
country: United States
facility: Site 5
state: South Carolina
city: Dallas
country: United States
facility: Site 51
state: Texas
city: El Paso
country: United States
facility: Site 3
state: Texas
city: Houston
country: United States
facility: Site 65
state: Texas
city: Shavano Park
country: United States
facility: Site 56
state: Texas
city: Everett
country: United States
facility: Site 31
state: Washington
city: Vienna
country: Austria
facility: Site 47
city: Sofia
country: Bulgaria
facility: Site 27
city: Halifax
country: Canada
facility: Site 70
state: Nova Scotia
city: Montréal
country: Canada
facility: Site 58
city: München
country: Germany
facility: Site 54
city: Würzburg
country: Germany
facility: Site 49
city: Jerusalem
country: Israel
facility: Site 30
city: Kfar Saba
country: Israel
facility: Site 29
city: Petach Tikva
country: Israel
facility: Site 28
city: Tel Aviv
country: Israel
facility: Site 69
city: Ancona
country: Italy
facility: Site 43
city: Messina
country: Italy
facility: Site 15
city: Milano
country: Italy
facility: Site 26
city: Napoli
country: Italy
facility: Site 12
city: Orbassano
country: Italy
facility: Site 38
city: Padova
country: Italy
facility: Site 67
city: Roma
country: Italy
facility: Site 40
city: Roma
country: Italy
facility: Site 16
city: Rotterdam
country: Netherlands
facility: Site 34
city: Bialystok
country: Poland
facility: Site 77
city: Chrzanów
country: Poland
facility: Site 37
city: Kraków
country: Poland
facility: Site 59
city: Lublin
country: Poland
facility: Site 33
city: Bucharest
country: Romania
facility: Site 66
city: Bucharest
country: Romania
facility: Site 63
city: Bucharest
country: Romania
facility: Site 64
city: Iaşi
country: Romania
facility: Site 73
city: Alicante
country: Spain
facility: Site 75
city: Girona
country: Spain
facility: Site 25
city: Madrid
country: Spain
facility: Site 24
city: Málaga
country: Spain
facility: Site 22
city: Sevilla
country: Spain
facility: Site 23
Study officials:
affiliation: Corcept Therapeutics
name: Andreas Moraitis, MD
role: STUDY_DIRECTOR
References:
citation: 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.