SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor (ACSPIRE)
Autonomous Cortisol Secretion (ACS), ACTH-Independent Cushing Syndrome, ACTH-Independent Adrenal Cushing Syndrome, Somatic
About this trial
This is an interventional treatment trial for Autonomous Cortisol Secretion (ACS) focused on measuring Autonomous Cortisol secretion (ACS), ACTH-independent adrenal Cushing's syndrome (aCs), benign adrenal tumor
Eligibility Criteria
Inclusion Criteria:
Diagnosis and main criteria for inclusion and exclusion:
The following are the main inclusion criteria:
- Adults able to provide informed consent.
- Documented characteristically benign adrenal nodule, with diameter ≤ 4 cm, homogenous texture, and non-contrast computerized tomography ≤ 20 HU attenuation or proven to be non malignant.
Diagnosis of diabetes mellitus, pre-diabetes or impaired glucose tolerance, either untreated or on stable standard of care treatment, based on at least one of:
- HbA1c ≥ 5.7% but not > 9.5%
- 2-hour glucose level ≥ 7.8 mmol (140 mg/dL) on a 75 g OGTT
At least one additional documented cortisol-related morbidities, either untreated or on stable standard of care treatment:
- hypercholesterolemia with total cholesterol > 3.9 mM (150 mg/dL);
- hypertriglyceridemia with triglycerides > 2.3 mM (200 mg/dL);
- osteopenia with bone densitometry Z-score < -2.0 or T-score < -1.0;
- history or evidence of minimally traumatic or osteoporotic fracture; or
- hypertension with resting supine blood pressure > 130 but < 180 mmHg systolic or > 85 but < 120 mmHg diastolic.
Poorly suppressible hypercortisolemia:
- Morning serum cortisol > 50 nM (1.8 mcg/dL) after a 1 mg ONDST.
- Subjects with dexamethasone < 3.3 nmol/L (130 ng/dL) will undergo a high-dose (8 mg) ONDST.
- Subjects who take estrogen-containing medicines will be evaluated based on free cortisol > 2.2 nM (80 ng/dL).
- For subjects with morning serum cortisol > 138 nM (5.0 mcg/dL) after ONDST, the Investigator will assess for adrenal Cushing's syndrome.
Exclusion Criteria:
- Diagnosis of ACTH-dependent Cushing's syndrome, pheochromocytoma, aldosteronoma, adrenocortical carcinoma, or congenital adrenal hyperplasia, or other malignancy associated hypercortisolism including history of adrenal carcinoma.
- History of adrenalectomy or planned adrenalectomy within 4 months after randomization.
- Exogenous hypercortisolism.
- Uncontrolled, clinically significant hypo- or hyperthyroidism.
- History of idiopathic thrombocytopenia.
- Moderately impaired renal function (estimated glomerular filtration rate < 60 mL/min/1.73m2).
- History of cancer (other than non-melanoma skin, thyroid, or early-stage prostate cancer) within 3 years.
- Any major surgery, or significant post-operative sequelae, within 1 month prior to informed consent or planned during the trial.
- Pregnant or lactating.
- Positive test for severe acute respiratory syndrome coronavirus 2 infection within 4 weeks, or hospitalization for Coronavirus disease 2019 within 6 months, prior to randomization.
- Any other current or prior medical condition expected to interfere with the conduct of the trial or the evaluation of its results.
- Participation in any clinical trial within 3 months prior to the first dose of study drug, or longer depending on half-life of the investigational therapy.
Sites / Locations
- Kaiser Permanente LAMC
- IU Simon Cancer Center - Indiana UniversityRecruiting
- University of Michigan
- Mayo Clinic Cancer Center (MCCC) - RochesterRecruiting
- Washington University School of Medicine - Center for Advanced Medicine (CAM) - Diabetes Center
- Ohio State McCampbell Outpatient CareRecruiting
- Rhode Island HospitalRecruiting
- Eastern Virginia Medical School - Strelitz Diabetes Center
- Chu AngersRecruiting
- CHU Hôpitaux de RouenRecruiting
- Hospices Civils of LyonRecruiting
- Lille University HospitalRecruiting
- Hôpital de la ConceptionRecruiting
- CHU Bordeaux Hopital HautRecruiting
- C.M.D.T.A. NeomedRecruiting
- Institutul National de EndocrinologieRecruiting
- Spitalul Clinic Judeţean de Urgenţe "Sf. Spiridon"
- Universitatea de Medicina si Farmacie Targu Mures - Spitalul Clinic Judetean de Urgenta Targu Mures
- University Hospital of WalesRecruiting
- Leeds Teaching Hospitals NHS TrustRecruiting
- King's College HospitalRecruiting
- The Christie NHS Foundation Trust
- Manchester University NHS Foundation Trust - Wythenshawe Hospital
- Salford Royal NHS Foundation TrustRecruiting
- University Hospital Southampton NHS Foundation Trust - Southampton General HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Experimental
Experimental
Experimental
Experimental
Placebo Comparator
SPI-62 dose 1
SPI-62 dose 2
SPI-62 dose 3
SPI-62 dose 4
Placebo
0.2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
0.6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks.
Placebo by mouth each morning for up to 12 weeks.