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

Sponsor
Corcept Therapeutics (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03697109
Collaborator
(none)
130
Enrollment
69
Locations
3
Arms
49.5
Anticipated Duration (Months)
1.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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 and/or uncontrolled hypertension

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed 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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
130 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Oct 16, 2018
Anticipated Primary Completion Date :
Nov 1, 2022
Anticipated Study Completion Date :
Dec 1, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Relacorilant (open-label phase)

The dose of relacorilant will be increased sequentially from 100 mg orally once daily to a target dose of 400 mg once daily.

Drug: Relacorilant
Relacorilant is supplied as 100 mg capsules for oral dosing.
Other Names:
  • CORT125134

    		•
    Experimental: Relacorilant (randomized-withdrawal phase)

    Patients who meet any of the response criteria will advance to the randomized-withdrawal phase of the study and receive the same highest dose as in the open-label phase.

    Drug: Relacorilant
    Relacorilant is supplied as 100 mg capsules for oral dosing.
    Other Names:
  • CORT125134

    		•
    Placebo Comparator: Placebo (randomized-withdrawal phase)

    Placebo matched to study drug

    Other: Placebo
    Placebo matched to study drug

    Outcome Measures

    Primary Outcome Measures

    1. 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)]

    2. In patients with hypertension, the proportion of patients with a loss of response with respect to hypertension from visit OL22 to RW12 [Week OL22 to Week 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

    3. 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 Outcome Measures

    1. 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)]

    2. 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]

    3. In patients with hypertension the mean change in SBP or DBP as compared between relacorilant and placebo [Week OL22 to week RW12]

    4. 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 [Week OL22 to week RW12]

      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.

    5. 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]

    6. 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 [Week OL22 to Week RW12]

      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

    7. 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)]

    8. In patients with IGT, the mean change in 2-hour oGTT glucose from Baseline to Visit OL22/ET [Baseline to week OL22 or ET]

    9. 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]

    10. In patients with uncontrolled hypertension the mean change in SBP or DBP from Baseline to visit OL22/ET [Baseline to week OL22 or ET]

      Blood pressure will be measured by 24 hour ABPM readings

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Site 21 Phoenix Arizona United States 85013
    2 Site 36 Los Angeles California United States 90095
    3 Site 42 Santa Monica California United States 90404
    4 Site 68 Torrance California United States 90502
    5 Site 9 Aurora Colorado United States 80045
    6 Site 32 Washington District of Columbia United States 20010
    7 Site 52 Gainesville Florida United States 32610
    8 Site 10 Miami Florida United States 33136
    9 Site 14 Atlanta Georgia United States 30318
    10 Site 41 Chicago Illinois United States 60611
    11 Site 7 Indianapolis Indiana United States 46202
    12 Site 2 Metairie Louisiana United States 70006
    13 Site 45 Baltimore Maryland United States 21205
    14 Site 46 Boston Massachusetts United States 02115
    15 Site 20 Ann Arbor Michigan United States 48109
    16 Site 4 Jackson Mississippi United States 39202
    17 Site 13 Saint Louis Missouri United States 63110
    18 Site 53 Omaha Nebraska United States 68198
    19 Site 8 Albany New York United States 12203
    20 Site 6 Jamaica New York United States 11432
    21 Site 57 New York New York United States 10021
    22 Site 35 New York New York United States 10029
    23 Site 39 New York New York United States 10065
    24 Site 1 Wilmington North Carolina United States 28401
    25 Site 44 Cleveland Ohio United States 44195
    26 Site 17 Columbus Ohio United States 43210
    27 Site 11 Oklahoma City Oklahoma United States 73104
    28 Site 62 Philadelphia Pennsylvania United States 19107
    29 Site 19 Pittsburgh Pennsylvania United States 15212
    30 Site 5 Summerville South Carolina United States 29485
    31 Site 51 Dallas Texas United States 75390
    32 Site 3 El Paso Texas United States 79935
    33 Site 18 Houston Texas United States 77030
    34 Site 65 Houston Texas United States 77079
    35 Site 56 Shavano Park Texas United States 78231
    36 Site 31 Everett Washington United States 98201
    37 Site 60 Graz Austria 8036
    38 Site 47 Vienna Austria 1090
    39 Site 27 Sofia Bulgaria 1431
    40 Site 55 Vancouver British Columbia Canada V6Z 1Y6
    41 Site 58 Montréal Canada H2X 0A9
    42 Site 50 Leipzig Germany 04103
    43 Site 54 München Germany 80336
    44 Site 49 Würzburg Germany 97080
    45 Site 30 Jerusalem Israel 911120
    46 Site 29 Kfar Saba Israel 4428164
    47 Site 28 Petach Tikva Israel 4941480
    48 Site 70 Tel Aviv Israel
    49 Site 43 Ancona Italy 60030
    50 Site 15 Messina Italy 98125
    51 Site 26 Milano Italy 20149
    52 Site 12 Napoli Italy 80131
    53 Site 38 Orbassano Italy 10043
    54 Site 67 Padova Italy 35128
    55 Site 40 Roma Italy 00161
    56 Site 16 Roma Italy 00189
    57 Site 48 Torino Italy 10126
    58 Site 34 Rotterdam Netherlands 3015 AA
    59 Site 37 Chrzanów Poland 32-500
    60 Site 59 Kraków Poland 31- 501
    61 Site 33 Lublin Poland 20-412
    62 Site 66 Bucharest Romania 010825
    63 Site 63 Bucharest Romania 011863
    64 Site 64 Bucharest Romania 011863
    65 Site 61 Barcelona Spain 08041
    66 Site 25 Girona Spain 17007
    67 Site 24 Madrid Spain 28007
    68 Site 22 Málaga Spain 29006
    69 Site 23 Sevilla Spain 41013

    Sponsors and Collaborators

    • Corcept Therapeutics

    Investigators

    • Study Director: Andreas Moraitis, MD, Corcept Therapeutics

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Corcept Therapeutics
    ClinicalTrials.gov Identifier:
    NCT03697109
    Other Study ID Numbers:
    • CORT125134-455
    First Posted:
    Oct 5, 2018
    Last Update Posted:
    Jul 20, 2022
    Last Verified:
    Jul 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Corcept Therapeutics
    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
    Additional relevant MeSH terms:
    Cushing Syndrome
    Syndrome

    Study Results

    No Results Posted as of Jul 20, 2022