Global Safety and Efficacy Registration Study of Crinecerfont in Pediatric Patients With Classic Congenital Adrenal Hyperplasia (CAHtalyst Pediatric Study)

Study Overview
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Brief Summary
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This is a Phase 3 study to evaluate the efficacy, safety, and tolerability of crinecerfont versus placebo administered for 28 weeks in approximately 81 pediatric participants with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The study consists of a 28-week double blind, placebo-controlled period, followed by 24 weeks of open-label treatment with crinecerfont. Subsequently, participants may elect to participate in the open-label extension (OLE) period. The duration of participation in the study is approximately 14 months for the core study and will be a variable amount of time per participant for the OLE (estimated to be approximately 3 years).

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Crinecerfont (NBI-74788) in Pediatric Subjects With Classic Congenital Adrenal Hyperplasia, Followed by Open-Label Treatment

Conditions
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Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: Crinecerfont
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be willing and able to adhere to the study procedures, including all requirements at the study center, and return for the follow-up visit. Have a medically confirmed diagnosis of 21-hydroxylase deficiency CAH. Be on a stable regimen of steroidal treatment for CAH. Have elevated androgen levels. Participants of childbearing potential must be abstinent or agree to use appropriate birth control during the study. Exclusion Criteria: Have a diagnosis of any of the other forms of classic CAH. Have a history of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy. Have a clinically significant unstable medical condition or chronic disease other than CAH. Have a history of cancer unless considered to be cured. Have a known history of clinically significant arrhythmia or abnormalities on ECG. Have a known hypersensitivity to any corticotropin-releasing hormone antagonist. Have received an investigational drug within 30 days before initial screening or plan to use an investigational drug (other than the study drug) during the study. Have current substance dependence or substance (drug) or alcohol abuse. Have had a significant blood loss or donated blood or blood products within 8 weeks prior to the study.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crinecerfont<br>Crinecerfont solution or capsule, administered orally, twice daily for 28 weeks during the placebo-controlled treatment period, followed by active treatment with crinecerfont for at least 24 weeks. | Drug: Crinecerfont<br>* CRF1-receptor antagonist<br>* Other names: NBI-74788;|
| Placebo Comparator: Placebo<br>Placebo solution or capsule, administered orally, twice daily for 28 weeks, followed by active treatment with crinecerfont for at least 24 weeks. | Drug: Crinecerfont<br>* CRF1-receptor antagonist<br>* Other names: NBI-74788;Drug: Placebo<br>* Non-active dosage form<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Serum Androstenedione (A4) at Week 4 |  | Baseline to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Serum 17-hydroxyprogesterone (17-OHP) at Week 4 |  | Baseline to Week 4 | 
| Percent Change from Baseline in Glucocorticoid Daily Dose at Week 28 |  | Baseline to Week 28 | 
| Achievement of a reduction in glucocorticoid daily dose to physiologic levels at Week 28 |  | Baseline to Week 28 | 
| Change from baseline in body mass index at Week 28 |  | Baseline to Week 28 | 
| Change from baseline in salivary 17-OHP at Week 28 |  | Baseline to Week 28 | 
| Change in bone age advancement at Week 28 |  | Baseline to Week 28 | 
| Change from baseline in predicted adult height at Week 52 |  | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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classic congenital adrenal hyperplasia (CAH), 21-hydroxylase deficiency