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

Study Overview
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Brief Summary
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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
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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.

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

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

Intervention / Treatment
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* Drug: SPI-62
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Staggered parallel crossover
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPI-62<br>Active drug by mouth each morning for up to 12 weeks | Drug: SPI-62<br>* 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor<br>Drug: Placebo<br>* Inactive tablets identical to SPI-62 tablets<br>|
| Placebo Comparator: Placebo<br>Placebo by mouth each morning for up to 12 weeks | Drug: SPI-62<br>* 11β hydroxysteroid dehydrogenase type 1 (HSD-1) inhibitor<br>Drug: Placebo<br>* Inactive tablets identical to SPI-62 tablets<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cushing's Syndrome, ACTH Secretion, Cushing's Disease, Excessive Cortisol secretion, Cortisol, ectopic CRH secretion