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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cortisol; Hypersecretion; Cortisol Overproduction; Cushing's Syndrome I; Cushing Disease Due to Increased ACTH Secretion; Cortisol Excess; Ectopic ACTH Secretion
• Intervention / Treatment: Drug: SPI-62; Drug: Placebo

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 Type: Interventional
• Enrollment (Estimated): 26
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Frank Czerwiec, MD; Phone Number: +1-617-465-0328; Email: fczerwiec@sparrowpharma.com
• Study Contact Backup: Name: Sarah Hooper; Phone Number: +1-617-465-0328; Email: shooper@sparrowpharma.com

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4002
    • Medical University of Plovdiv
  • Sofia, Bulgaria, 1431
    • Clinical Center of Endocrinology and Gerontology, University Hospital of Endocrinology, Medical University Sofia (USHATE)
  • Sofia, Bulgaria, 1431
    • Medical University of Sofia
• Romania
  • Bucharest, Romania, 050474
    • Carol Davila University of Medicine and Pharmacy
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Joseph's Hospital and Medical Center - Barrow Neurological Institute (BNI) - Pituitary Center
  • Florida
    • Fort Myers, Florida, United States, 33907
      • Southwest General Healthcare Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Cancer Center (MCCC) - Rochester
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School Of Medicine - Center For Advanced Medicine (CAM)
  • Nevada
    • Henderson, Nevada, United States, 89052
      • Comprehensive and Interventional Pain Management Llp
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU) - Northwest Pituitary Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh Medical Center

Participation Criteria

Eligibility Criteria

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

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2022
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: March 23, 2022
• First Submitted That Met QC Criteria: March 23, 2022
• First Posted (Actual): April 1, 2022

Study Record Updates

• Last Update Posted (Actual): April 19, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Cortisol; Cushing's Syndrome; Cushing's Disease; ACTH Secretion; Excessive Cortisol secretion; ectopic CRH secretion
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Endocrine System Diseases; Disease; Endocrine Gland Neoplasms; Hypothalamic Diseases; Paraneoplastic Syndromes; Hyperpituitarism; Pituitary Diseases; Adenoma; Adrenal Gland Diseases; Pituitary Neoplasms; Paraneoplastic Endocrine Syndromes; Syndrome; Cushing Syndrome; Adrenocortical Hyperfunction; ACTH-Secreting Pituitary Adenoma; Pituitary ACTH Hypersecretion; ACTH Syndrome, Ectopic
• Other Study ID Numbers: SPI-62-CL-2001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No