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

This is 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.

Study Overview

• Status: Completed
• Conditions: Autonomous Cortisol Secretion (ACS); ACTH-Independent Cushing Syndrome; ACTH-Independent Adrenal Cushing Syndrome, Somatic
• Intervention / Treatment: Drug: SPI-62 dose

Detailed Description

This is a multicenter, open-label, single-arm study, 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Romania
  • Brasov, Romania, 500283
    • C.M.D.T.A. Neomed
  • Bucharest, Romania, 11863
    • Institutul National de Endocrinologie
• United Kingdom
  • London, United Kingdom, SW9 8RR
    • King's College Hospital
• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center (MCCC) - Rochester
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State McCampbell Outpatient Care

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SPI-62 dose; 2mg dose level of SPI-62. Active drug by mouth.	Drug: SPI-62 dose; SPI-62 is an 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor, supplied as oral tablets for dose 2 of drug (2mg).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sparrow Pharmaceuticals
• Investigators: Study Chair: Frank Czerwiec, MD, Sparrow Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): December 1, 2024
• Study Completion (Actual): February 18, 2025

Study Registration Dates

• First Submitted: June 23, 2022
• First Submitted That Met QC Criteria: June 23, 2022
• First Posted (Actual): June 29, 2022

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Autonomous Cortisol secretion (ACS); ACTH-independent adrenal Cushing's syndrome (aCs); benign adrenal tumor
• Additional Relevant MeSH Terms: Endocrine System Diseases; Pathologic Processes; Neoplasms by Site; Neoplasms; Disease; Endocrine Gland Neoplasms; Adrenal Gland Diseases; Acth-Independent Macronodular Adrenal Hyperplasia
• Other Study ID Numbers: SPI-62-CL-2002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No