SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor

Study Overview
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Brief Summary
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This will be a study with SPI-62 to evaluate the efficacy, safety, and pharmacological effect of SPI-62 in subjects with hypercortisolism related to a benign adrenal tumor. Each subject will receive 2mg of SPI-62 daily.

Detailed Description
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This is a multicenter, Phase 2 study to estimate SPI-62's effect on clinical features of hypercortisolism related to a benign adrenal tumor, including diabetes/impaired glucose tolerance, hyperlipidemia, hypertension, and osteopenia. Each subject who provides consent and meets all inclusion and exclusion criteria will participate in a screening period and an open-ended treatment period. Visits occur at screening/baseline, months 1, 3, 6, 9, and 12, and then quarter-annually.

Official Title
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SPI-62 as a Treatment for Hypercortisolism Related to a Benign Adrenal Tumor

Conditions
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Autonomous Cortisol Secretion (ACS), ACTH-Independent Cushing Syndrome, ACTH-Independent Adrenal Cushing Syndrome, Somatic

Intervention / Treatment
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* Drug: SPI-62 dose1
* Drug: SPI-62 dose 2
* Drug: SPI-62 dose 3
* Drug: SPI-62 dose 4
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPI-62 dose 1<br>0.2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks. | Drug: SPI-62 dose1<br>* SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 1 of drug (0.2mg).<br>|
| Experimental: SPI-62 dose 2<br>0.6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks. | Drug: SPI-62 dose 2<br>* SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (0.6mg).<br>|
| Experimental: SPI-62 dose 3<br>2mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks. | Drug: SPI-62 dose 3<br>* SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (2mg).<br>|
| Experimental: SPI-62 dose 4<br>6mg dose level of SPI-62. Active drug by mouth each morning for up to 12 weeks. | Drug: SPI-62 dose 4<br>* SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (6mg).<br>|
| Placebo Comparator: Placebo<br>Placebo by mouth each morning for up to 12 weeks. | Drug: Placebo<br>* Inactive tablets identical to SPI-62 tablets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c at Week 6 | HbA1c change from baseline | Baseline to week 6 | 
| Change in HbA1c at week 12 | HbA1c change from baseline | Baseline to week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autonomous Cortisol secretion (ACS), ACTH-independent adrenal Cushing's syndrome (aCs), benign adrenal tumor