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

NCT05307328 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: SPI-62-CL-2001
• Study Type: interventional
• Target: 26
• Locations: 3 countries
• Sites: 12

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.

Conditions

Cushing's Syndrome I; Cushing Disease Due to Increased ACTH Secretion; Cortisol Excess; Cortisol; Hypersecretion; Cortisol Overproduction; Ectopic ACTH Secretion

Keywords

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Treatment emergent adverse events

  Baseline through 24 weeks of treatment

Study Arms (2)

SPI-62

EXPERIMENTAL

Active drug by mouth each morning for up to 12 weeks

Drug: SPI-62; Drug: Placebo

Placebo

PLACEBO COMPARATOR

Placebo by mouth each morning for up to 12 weeks

Drug: SPI-62; Drug: Placebo

Interventions

SPI-62 DRUG

11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor

Placebo; SPI-62

Placebo DRUG

Inactive tablets identical to SPI-62 tablets

Placebo; SPI-62

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or non-menstruating female
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sparrow Pharmaceuticals: lead

Study Sites (12)

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

Phoenix, Arizona, 85013, United States

Location

Southwest General Healthcare Center

Fort Myers, Florida, 33907, United States

Location

Mayo Clinic Cancer Center (MCCC) - Rochester

Rochester, Minnesota, 55905, United States

Location

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

St Louis, Missouri, 63110, United States

Location

Comprehensive and Interventional Pain Management Llp

Henderson, Nevada, 89052, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

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

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Medical University of Plovdiv

Plovdiv, 4002, Bulgaria

Location

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

Sofia, 1431, Bulgaria

Location

Medical University of Sofia

Sofia, 1431, Bulgaria

Location

Carol Davila University of Medicine and Pharmacy

Bucharest, 050474, Romania

Location

MeSH Terms

Conditions

ACTH Syndrome, Ectopic; Cushing Syndrome; Pituitary ACTH Hypersecretion

Condition Hierarchy (Ancestors)

Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Neoplasms; Adrenocortical Hyperfunction; Adrenal Gland Diseases; Endocrine System Diseases; Hyperpituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Frank Czerwiec, MD

  Sparrow Pharmaceuticals (info@sparrowpharma.com)

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Staggered parallel crossover

Study Record Dates

• First Submitted: March 23, 2022
• First Posted: April 1, 2022
• Study Start: September 1, 2022
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: October 8, 2025

Record last verified: 2025-05

Locations

US (8); RO (1); BU (3)