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

• ClinicalTrials.gov Identifier: NCT05307328
• Recruitment Status: Active, not recruiting
• First Posted: April 1, 2022
• Last Update Posted: April 19, 2024
• Sponsor: Sparrow Pharmaceuticals
• Information provided by (Responsible Party): Sparrow Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cushing's Syndrome I; Cushing Disease Due to Increased ACTH Secretion; Cortisol Excess; Cortisol; Hypersecretion; Cortisol Overproduction; Ectopic ACTH Secretion	Drug: SPI-62; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 26 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Staggered parallel crossover
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: SPI-62 as a Treatment for Adrenocorticotropic Hormone-dependent Cushing's Syndrome
• Actual Study Start Date: September 1, 2022
• Estimated Primary Completion Date: December 1, 2024
• Estimated Study Completion Date: December 1, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: SPI-62; Active drug by mouth each morning for up to 12 weeks	Drug: SPI-62; 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor; Drug: Placebo; Inactive tablets identical to SPI-62 tablets
Placebo Comparator: Placebo; Placebo by mouth each morning for up to 12 weeks	Drug: SPI-62; 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor; Drug: Placebo; Inactive tablets identical to SPI-62 tablets

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in urinary HSD-1 ratio [ Time Frame: 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 :

1. Treatment emergent adverse events [ Time Frame: 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

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

St. Joseph's Hospital and Medical Center - Barrow Neurological Institute (BNI) - Pituitary Center

Phoenix, Arizona, United States, 85013

United States, Florida

Southwest General Healthcare Center

Fort Myers, Florida, United States, 33907

United States, Minnesota

Mayo Clinic Cancer Center (MCCC) - Rochester

Rochester, Minnesota, United States, 55905

United States, Missouri

Washington University School of Medicine - Center for Advanced Medicine (CAM)

Saint Louis, Missouri, United States, 63110

United States, Nevada

Comprehensive and Interventional Pain Management Llp

Henderson, Nevada, United States, 89052

United States, New York

Memorial Sloan-Kettering Cancer Center

New York, New York, United States, 10065

United States, Oregon

Oregon Health & Science University (OHSU) - Northwest Pituitary Center

Portland, Oregon, United States, 97239

United States, Pennsylvania

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States, 15213

Bulgaria

Medical University of Plovdiv

Plovdiv, Bulgaria, 4002

Clinical Center of Endocrinology and Gerontology, University Hospital of Endocrinology, Medical University Sofia (USHATE)

Sofia, Bulgaria, 1431

Medical University of Sofia

Sofia, Bulgaria, 1431

Romania

Carol Davila University of Medicine and Pharmacy

Bucharest, Romania, 050474

Sponsors and Collaborators

Sparrow Pharmaceuticals

Investigators

• Study Director: Frank Czerwiec, MD; Sparrow Pharmaceuticals (info@sparrowpharma.com)

More Information

• Responsible Party: Sparrow Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT05307328
• Other Study ID Numbers: SPI-62-CL-2001
• First Posted: April 1, 2022
• Last Update Posted: April 19, 2024
• Last Verified: April 2024

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Sparrow Pharmaceuticals:

Cushing's Syndrome; ACTH Secretion; Cushing's Disease; Excessive Cortisol secretion; Cortisol; ectopic CRH secretion

Additional relevant MeSH terms:

ACTH-Secreting Pituitary Adenoma; ACTH Syndrome, Ectopic; Pituitary ACTH Hypersecretion; Cushing Syndrome; Adrenocortical Hyperfunction; Syndrome; Disease; Pathologic Processes; Adrenal Gland Diseases; Endocrine System Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Pituitary Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes