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

This Phase 2, open-label, sequential dose cohort study will evaluate the efficacy, safety, PK, and PD of atumelnant (CRN04894) when administered for 12 weeks in participants with CAH caused by 21-hydroxylase deficiency. Up to 42 participants will be enrolled in the study.

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). For Cohort 4, a mean daily dose of ≥11 mg/m²/day of hydrocortisone or hydrocortisone equivalents will be used for inclusion
• 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 for Cohorts 1-3. In Cohort 4, dexamethasone is permitted
• 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