A Ph2b to Evaluate Tildacerfont in the Reduction of Glucocorticoid Steroid Doses in Adult CAH

Study Overview
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Brief Summary
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An investigation of the ability of Tildacerfont to reduce supraphysiologic glucocorticoid dosing in classic CAH subjects up to 76 weeks of treatment. Optional open label extension up to 240 weeks.

Detailed Description
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This is a study that will evaluate the ability of Tildacerfont to reduce the glucocorticoid steroid dose used by adult CAH subjects. The first 24-weeks will be a double-blind, placebo controlled, comparison of Tildacerfont vs Placebo. The following 52-weeks will allow all subjects to move to open label Tildacerfont to continue to reduce steroid dose where appropriate, and observe long term safety. Subjects will be offered a long term open label extension up to 240 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) in Reducing Supraphysiologic Glucocorticoid Use in Adult Subjects With Classic Congenital Adrenal Hyperplasia

Conditions
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Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: Tildacerfont/Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects over 18 years old, inclusive Has a documented historical diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented elevated 17-OHP and currently treatment with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs) Has been on a stable, supraphysiologic dose of GC replacement for ≥1 month before screening. For subjects with the salt-wasting form of CAH, subject has been on a stable dose of mineralocorticoid replacement for ≥1 month before screening Exclusion Criteria: Has a known or suspected diagnosis of any other known form of classic CAH (not due to 21-hydroxylase deficiency) Has a history that includes bilateral adrenalectomy or hypopituitarism Has a history of allergy or hypersensitivity to tildacerfont, any of its excipients, or any other CRF1 receptor antagonist Shows clinical signs or symptoms of adrenal insufficiency

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: Parallel Assignment
Interventional Model Description: Subjects will be randomized in a 1:1 manner to either Tildacerfont or Placebo for 24 weeks followed by 52 weeks open label Tildacerfont
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tildacerfont Group<br>Tildacerfont administered daily via oral tablet for 24 weeks at dose level 1; followed by open label tildacerfont for 52 weeks | Drug: Tildacerfont/Placebo<br>* Tablet, administered daily<br>* Other names: SPR001;|
| Placebo Comparator: Placebo<br>Placebo administered daily via oral tablet for 24 weeks; followed by open label tildacerfont for 52 weeks | Drug: Tildacerfont/Placebo<br>* Tablet, administered daily<br>* Other names: SPR001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who can reduce GC dose at Week 24 | Proportion of subjects with at least a 5 mg/day HCe reduction from baseline in GC dose and A4 ≤ULN at Week 24 | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage change in GC use in subjects with CAH | Percent change from baseline in GC dose at week 24 | 24 weeks | 
| Change in the median cumulative HCe dose in subjects with CAH | Median total cumulative GC dose in HCe at Week 24 | 24 Weeks | 
| Effectiveness in reducing cardiovascular risk in subjects with CAH | Proportion of subjects with improvement in at least one cardiovascular risk factor at week 24 | 24 Weeks | 
| Effectiveness in improving HOMA-IR in subjects with CAH | Change from baseline in the HOMA-IR at Week 24 | 24 Weeks | 
| Effect on body weight in subjects with CAH | Percent change from baseline in body weight after 24 weeks of tildacerfont treatment | 24 weeks | 
| Effect on body weight in subjects with CAH | Percent change from baseline in body weight after 52 weeks of tildacerfont treatment | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CAH, Adrenal Disorder, Congenital Adrenal Hyperplasia