Global Safety and Efficacy Registration Study of Crinecerfont for Congenital Adrenal Hyperplasia

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 24 weeks in approximately 165 adult participants with classic CAH due to 21-hydroxylase deficiency. The study consists of a 6-month randomized, double-blind, placebo-controlled period, followed by 1 year 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 20 months for the core study and will be a variable amount of time per subject 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 Adult 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 classic 21-hydroxylase deficiency CAH. Be on a stable regimen of steroidal treatment for CAH. Participants of childbearing potential must agree to use an acceptable method of contraception during the study. Exclusion Criteria: Have a diagnosis of any of the other known 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 cured. Are pregnant. Have a known history of clinically significant arrhythmia or abnormalities on ECG. Have a known hypersensitivity to any corticotropin releasing hormone antagonists. Have received any other 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 current substance (drug) or alcohol abuse. Have had a blood loss ≥550 mL or donated blood or blood products within 8 weeks prior to the study.

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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Crinecerfont<br>Crinecerfont capsule, administered orally, twice daily for 24 weeks during the placebo-controlled treatment period, followed by active treatment with crinecerfont for at least 1 year. | Drug: Crinecerfont<br>* CRF1-receptor antagonist<br>* Other names: NBI-74788;|
| Placebo Comparator: Placebo<br>Placebo capsule, administered orally, twice daily for 24 weeks, followed by active treatment with crinecerfont for at least 1 year. | 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 |
| --- | --- | --- |
| Percent change from baseline in glucocorticoid daily dose at Week 24 |  | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in serum androstenedione at Week 4 |  | Baseline and Week 4 | 
| Achievement of a reduction in glucocorticoid daily dose to physiologic levels at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in homeostatic model assessment of insulin resistance (HOMA-IR) index at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in body weight at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in fat mass at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in blood pressure at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in glucose tolerance at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in waist circumference at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in menstrual regularity at Week 24 |  | Baseline and Week 24 | 
| Change from baseline in testicular adrenal rest tumor size at Week 24 |  | Baseline and Week 24 |