A Phase 2 Study to Evaluate the Safety, Efficacy and PK of Tildacerfont in Children With CAH

Study Overview
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Brief Summary
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An investigation of the safety and efficacy of tildacerfont in pediatric subjects with CAH.

Detailed Description
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This is a study to evaluate the safety and efficacy of tildacerfont in pediatric subjects with Congenital Adrenal Hyperplasia (CAH). Treatment will consist of 12 weeks of continuous dosing followed by safety follow up.

Official Title
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A Phase 2 Study to Evaluate the Safety, Efficacy and Pharmacokinetics of SPR001 (Tildacerfont) in Children Aged 2 to 17 Years With Congenital Adrenal Hyperplasia

Conditions
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Congenital Adrenal Hyperplasia, 21-OHD

Intervention / Treatment
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* Drug: Tildacerfont


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects aged 2 to 17 years Diagnosis of CAH due to 21-hydroxylase deficiency (OHD) and/or elevated 17- hydroxyprogesterone (OHP) requiring ongoing GC replacement since diagnosis Stable dose of GC replacement for at least 1 month prior to screening Exclusion Criteria: CAH not due to 21-OHD History of bilateral adrenalectomy or hypopituitarism Clinically significant unstable medical conditions, illness, or chronic diseases History of active bleeding disorders Females who are pregnant or nursing

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 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: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Subjects will be assigned to treatment cohorts by age.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: Age 11-17 Treatment with Tildacerfont<br>Oral Tildacerfont administered daily for 12 consecutive weeks. | Drug: Tildacerfont<br>* Oral tablet formulation taken once daily in combination with glucocorticoid therapy.<br>* Other names: SPR001;|
| Experimental: Cohort 2: Age 11-17 Treatment with Tildacerfont<br>Oral Tildacerfont administered daily for 12 consecutive weeks. | Drug: Tildacerfont<br>* Oral tablet formulation taken once daily in combination with glucocorticoid therapy.<br>* Other names: SPR001;|
| Experimental: Cohort 3: Age 2-10 Treatment with Tildacerfont<br>Oral Tildacerfont administered daily for 12 consecutive weeks. | Drug: Tildacerfont<br>* Oral tablet formulation taken once daily in combination with glucocorticoid therapy.<br>* Other names: SPR001;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of subjects with Treatment-emergent adverse event (TEAE) as assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 | To evaluate safety of tildacerfont in pediatric subjects with CAH as measured by number of subjects with adverse events following dosing by CTCAE version 5.0 | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects who achieve reduction in androstenedione (A4) or reduction in glucocorticoid (GC) dosing | To determine the efficacy of tildacerfont on disease control or reduction of GC use in pediatric subjects with classic CAH as measured by number of subjects who achieve a reduction in A4 or reduction in GC dosing at week 12 | 12 weeks | 
| Proportion of subjects with elevated baseline A4 who achieve a reduction in A4 | To determine the efficacy of tildacerfont on disease control in pediatric subjects with classic CAH measured by the number of subjects with elevated baseline A4 who achieve reduction in A4 at week | 4 weeks | 
| Tildacerfont pharmacokinetics (PK) | To determine the consistency of preliminary tildacerfont PK in pediatric subjects with those simulated in a PBPK model measured by comparing tildacerfont plasma concentrations with current PBPK simulation for consistency | 12 weeks | 

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