SPI-62 As a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome

Phase 2

Active, not recruiting

• Conditions: Cortisol Excess; Cortisol Overproduction; Cushing's Syndrome I; Cushing Disease Due to Increased ACTH Secretion; Cortisol; Hypersecretion; Ectopic ACTH Secretion
• Interventions: Drug: SPI-62; Drug: Placebo

• Registration Number: NCT05307328
• Lead Sponsor: Sparrow Pharmaceuticals

Brief Summary

This is a randomized, placebo-controlled, study of SPI-62 in subjects with ACTH-dependent Cushing's syndrome caused by a non-adrenal tumor. Subjects will receive each of the following 2 treatments for 24 weeks: SPI-62 and matching placebo with the option of long-term extension.

Detailed Description

This is a multicenter, randomized, placebo-controlled, Phase 2 study to evaluate the pharmacologic effect, efficacy, and safety of SPI-62 in subjects with ACTH-dependent Cushing's syndrome. Each subject who provides consent and meets all inclusion and exclusion criteria will participate in a screening period (Days -35 to -8), a baseline period (Days -7 to -1), and a treatment period (Day 1 of Week 1 to Day 168 ± 3 days of Week 24) and, the option of long-term extension. Subjects have the option to continue with the study on active study drug and return to the site every 3 months for blood tests and study drug dispensing. The visits may be conducted remotely if testing can be arranged.

Study Timeline

• Study First Submitted: 2022-03-23
• Study First Submitted QC: 2022-03-23
• Study First Posted: 2022-04-01
• Study Start: 2022-09-01
• Status Verified: 2024-04
• Last Update Submitted: 2025-03-13
• Last Update Posted: 2025-03-18
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• Male or non-menstruating female
• 18 years or older
• Active and consistent cortisol excess
• Documented diagnosis of ACTH-dependent Cushing's syndrome including Cushing's disease, ectopic ACTH secretion, and ectopic CRH secretion.

Exclusion Criteria

• Recent (within 6 weeks) surgery for Cushing's or surgery planned within 24 weeks of randomization.
• History of any fractionated radiation therapy for Cushing's within the past 2 years or conventional radiation therapy within 4 years.
• History of bilateral adrenalectomy or exogenous, pseudo, cyclic, or non-ACTH-dependent Cushing's syndrome (including certain inherited conditions).
• High risk of acute morbidity from corticotroph adenoma growth (similar to that which occurs with Nelson's syndrome) defined as current evidence of macroadenoma at risk of impingement of vital structures.
• Any current or prior medical condition, medical or surgical therapies, or clinical trial participation expected to interfere with the conduct of the study or the evaluation of its results, including but not limited to poor venous access or recent receipt or donation of blood products.
• Women who are currently pregnant, lactating or planning fertility and unwilling to adhere to approved contraceptives or abstinence.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
SPI-62	Placebo	Active drug by mouth each morning for up to 12 weeks
SPI-62	SPI-62	Active drug by mouth each morning for up to 12 weeks
Placebo	SPI-62	Placebo by mouth each morning for up to 12 weeks
Placebo	Placebo	Placebo by mouth each morning for up to 12 weeks

Primary Outcome Measures

Name	Time	Method
Change from baseline in urinary HSD-1 ratio	Baseline to 6 weeks	The urinary HSD-1 ratio (tetrahydrocortisol + allotetrahydrocortisol ) / tetrahydrocortisone will be used as a biomarker of HSD-1 activity in liver. The primary analysis will include only subjects with Cushing's disease.

Secondary Outcome Measures

Name	Time	Method
Treatment emergent adverse events	Baseline through 24 weeks of treatment	Adverse events including clinically significant abnormal values on clinical laboratory evaluations, continuous glucose monitoring (CGM), 12-lead ECGs, vital signs measurements (including orthostatic vital sign measurements), physical examinations, and HPA and HPG axis biomarkers

Trial Locations

Locations (12)

Southwest General Healthcare Center; 🇺🇸 Fort Myers, Florida, United States

University of Pittsburgh Medical Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

Clinical Center of Endocrinology and Gerontology, University Hospital of Endocrinology, Medical University Sofia (USHATE); 🇧🇬 Sofia, Bulgaria

Medical University of Sofia; 🇧🇬 Sofia, Bulgaria

Carol Davila University of Medicine and Pharmacy; 🇷🇴 Bucharest, Romania

Medical University of Plovdiv; 🇧🇬 Plovdiv, Bulgaria

Mayo Clinic Cancer Center (MCCC) - Rochester; 🇺🇸 Rochester, Minnesota, United States

St. Joseph's Hospital and Medical Center - Barrow Neurological Institute (BNI) - Pituitary Center; 🇺🇸 Phoenix, Arizona, United States

Washington University School of Medicine - Center for Advanced Medicine (CAM); 🇺🇸 Saint Louis, Missouri, United States

Comprehensive and Interventional Pain Management Llp; 🇺🇸 Henderson, Nevada, United States

Memorial Sloan-Kettering Cancer Center; 🇺🇸 New York, New York, United States

Oregon Health & Science University (OHSU) - Northwest Pituitary Center; 🇺🇸 Portland, Oregon, United States