Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 in Participants With Congenital Adrenal Hyperplasia

Study Overview
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Brief Summary
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The purpose of this Phase 2, open-label, sequential dose cohort study is to evaluate the safety, efficacy, and pharmacokinetics (PK) of CRN04894 in participants with classic congenital adrenal hyperplasia (CAH) caused by 21-hydroxylase deficiency.

Detailed Description
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This Phase 2, open-label, sequential dose cohort study will evaluate the efficacy, safety, PK, and PD of CRN04894 when administered for 12 weeks in participants with CAH caused by 21-hydroxylase deficiency. Up to approximately 30 participants will be enrolled in the study.

Official Title
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A 12-week, Phase 2 Open-label, Sequential Dose Cohort Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of CRN04894 Treatment in Participants With Congenital Adrenal Hyperplasia

Conditions
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Congenital Adrenal Hyperplasia, Classic Congenital Adrenal Hyperplasia

Intervention / Treatment
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* Drug: CRN04894


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female participants ≥18 to 75 years of age at the time of signing the Informed Consent Form (ICF). Participants ≥16 years of age may be included in sites located in the United States Classic 21-hydroxylase deficiency On a stable regimen of glucocorticoid replacement (eg, hydrocortisone, prednisolone, prednisone, methylprednisolone) Compliance with glucocorticoid replacement and mineralocorticoid replacement (if applicable) regimen during the Screening Period Minimum total daily dose of ≥15 mg hydrocortisone (or equivalent) If on estrogen therapy (any route), dose must be stable for at least 3 months prior to Screening Exclusion Criteria: Diagnosis of any other form of CAH other than classic 21-hydroxylase deficiency Dexamethasone use within 30 days of Screening History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic glucocorticoid therapy Night shift workers or any other reason for abnormal sleep/wake cycles Clinically significant unstable medical condition or chronic disease other than CAH History of major surgery/surgical therapy for any cause within 4 weeks prior to Screening Diabetes mellitus treated with insulin for less than 6 weeks prior to Screening, or with change in total daily insulin dose by >15% within 6 weeks prior to Screening Poorly controlled diabetes mellitus defined as having a hemoglobin A1c (HbA1c) ≥8.5%(≥69 mmol/mL), or estimated HbA1c based on fructosamine if HbA1c is not evaluable (eg, due to hemoglobinopathies) Participants with hypothyroidism who are not receiving adequate hormone replacement therapy based on thyroid hormone levels measured at the time of Screening History of unstable angina or acute myocardial infarction within 12 weeks prior to Screening or other clinically significant cardiac disease at the time of Screening History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ Pregnant or lactating Known history of illicit drug or alcohol abuse within the last year Use of antiandrogen therapy in the past 3 months (eg, spironolactone, finasteride, cyproterone acetate, flutamide) Use of testosterone, androgen-containing supplements, aromatase inhibitors, or growth hormone

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 75 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
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sequential Dose<br>Sequential, open-label, 12-week fixed-dose cohorts. | Drug: CRN04894<br>* CRN04894 is an orally active nonpeptide melanocortin 2 receptor (MC2R) or adrenocorticotropic hormone (ACTH) antagonist.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in morning (before 11:00) serum androstenedione (A4) |  | Week 12 | 
| Incidence of treatment-emergent adverse events (TEAEs) throughout the study |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in morning (before 11:00) serum 17-hydroxyprogesterone (17-OHP) |  | Week 12 |