A Ph2b to Evaluate Clinical Efficacy and Safety of Tildacerfont in Adult CAH

Study Overview
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Brief Summary
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An investigation of the efficacy and safety of up to 70 weeks of treatment with Tildacerfont in subjects with classic CAH who have elevated biomarkers at baseline on their current GC regimen. Optional open label treatment extension period up to 240 weeks with 200mg tildacerfont QD.

Detailed Description
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This is a study that will test the efficacy and safety of Tildacerfont. The first 12-weeks will be a double-blind, placebo controlled, dose ranging study. The following 58-weeks will assess the long term safety of Tildacerfont. Optional open label treatment extension period up to 240 weeks with 200mg tildacerfont QD.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate the Efficacy and Safety of SPR001 (Tildacerfont) 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 known childhood diagnosis of classic CAH due to 21-hydroxylase deficiency based on genetic mutation in CYP21A2 and/or documented elevated 17-OHP and currently treated with HC, HC acetate, prednisone, prednisolone, methylprednisolone (or a combination of the aforementioned GCs) Has been on a stable supraphysiologic dose of GC replacement ≥15 mg/day and ≤60 mg/day in HC equivalents 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 Current treatment with dexamethasone as GC therapy for CAH. Prior treatment with dexamethasone is allowed as long as the transition to an alternative GC regimen (eg, HC, prednisone, or prednisolone) has resulted in a stable dose of GC replacement for ≥1 month before screening. 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 1:1:1:1 manner to one of three doses of Tildacerfont or Placebo.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tildacerfont Group 1<br>Tildacerfont administered daily via oral tablet for 12 weeks at dose level 1 | Drug: Tildacerfont/Placebo<br>* Tablet, administered daily<br>* Other names: SPR001;|
| Experimental: Tildacerfont Group 2<br>Tildacerfont administered daily via oral tablet for 12 weeks at dose level 2 | Drug: Tildacerfont/Placebo<br>* Tablet, administered daily<br>* Other names: SPR001;|
| Experimental: Tildacerfont Group 3<br>Tildacerfont administered daily via oral tablet for 70 weeks at dose level 3 | Drug: Tildacerfont/Placebo<br>* Tablet, administered daily<br>* Other names: SPR001;|
| Placebo Comparator: Placebo<br>Placebo administered daily via oral tablet for 12 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 |
| --- | --- | --- |
| Change in androstenedione | Percent change of androstenedione | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve reduction A4 levels | Proportion of subjects who achieve A4 ≤ ULN | 12 weeks | 
| Proportion of subjects who achieve reduction in 17-OHP | Proportion of subjects who achieve 17-OHP≤ 1200ng/dL | 12 weeks | 
| Effectiveness in reducing TART(s) in Male CAH subjects | Change in lesion volume of TART(s) from baseline | 12 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