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

Cortisol; Hypersecretion Clinical Trial

— RESCUE  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05307328
• Other study ID #: SPI-62-CL-2001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: September 1, 2022
• Est. completion date: December 1, 2025

Study information

• Verified date: April 2024
• Source: Sparrow Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 26
• Est. completion date: December 1, 2025
• Est. primary completion date: December 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• ACTH-Secreting Pituitary Adenoma
• Adrenocortical Hyperfunction
• Cortisol Overproduction
• Cortisol; Hypersecretion
• Cushing Syndrome
• Pituitary ACTH Hypersecretion
• Syndrome

Intervention

Drug:
• SPI-62
11ß hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor
• Placebo
Inactive tablets identical to SPI-62 tablets

Locations

Country	Name	City	State
Bulgaria	Medical University of Plovdiv	Plovdiv
Bulgaria	Clinical Center of Endocrinology and Gerontology, University Hospital of Endocrinology, Medical University Sofia (USHATE)	Sofia
Bulgaria	Medical University of Sofia	Sofia
Romania	Carol Davila University of Medicine and Pharmacy	Bucharest
United States	Southwest General Healthcare Center	Fort Myers	Florida
United States	Comprehensive and Interventional Pain Management Llp	Henderson	Nevada
United States	Memorial Sloan-Kettering Cancer Center	New York	New York
United States	St. Joseph's Hospital and Medical Center - Barrow Neurological Institute (BNI) - Pituitary Center	Phoenix	Arizona
United States	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University (OHSU) - Northwest Pituitary Center	Portland	Oregon
United States	Mayo Clinic Cancer Center (MCCC) - Rochester	Rochester	Minnesota
United States	Washington University School of Medicine - Center for Advanced Medicine (CAM)	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Sparrow Pharmaceuticals

Countries where clinical trial is conducted

United States,  Bulgaria,  Romania, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in urinary HSD-1 ratio	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.	Baseline to 6 weeks
Secondary	Treatment emergent adverse events	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	Baseline through 24 weeks of treatment