Phase 3b Open‑Label Study of Crinecerfont (NBI‑74788) for Androgen Reduction in Adults with Classic Congenital Adrenal Hyperplasia

The primary objective is to assess the impact of oral crinecerfont on serum androstenedione concentrations in adults with classic congenital adrenal hyperplasia who have been maintained on a stable glucocorticoid regimen for at least six months. Reduction of this androgen precursor is intended to improve disease control and mitigate excess androgen‑related complications.

The trial enrolled 29 adults diagnosed with Classic Congenital Adrenal Hyperplasia. Both male and female participants were included; females were limited to 45 years of age or younger, while all participants were at least 18 years old. All subjects had a medically confirmed diagnosis of classic 21‑hydroxylase deficiency based on elevated 17‑OHP, CYP21A2 genotype, newborn screening, or cosyntropin stimulation testing. Participants were required to be on a stable glucocorticoid regimen for at least one month, using oral hydrocortisone, prednisone, prednisolone, or methylprednisolone with a morning dose. Those receiving fludrocortisone needed a stable dose and normal plasma renin activity, blood pressure, and electrolytes. Female participants of childbearing potential had to use effective contraception throughout the study. General health status required stable hormone levels, no orthostatic hypotension, and normal serum sodium and potassium. The population was selected through screening that confirmed the diagnostic criteria and medication stability, ensuring participants were otherwise healthy enough to meet study requirements.

The study is a Phase 3b open-label trial evaluating the effect of oral crinecerfont capsules on adrenal androgen excess in adults with Classic Congenital Adrenal Hyperplasia (CAH) who are on a stable glucocorticoid regimen. Eligible participants (≥18 years, female ≤45 years, confirmed 21‑hydroxylase deficiency, stable glucocorticoid dose ≥1 month) undergo a screening visit to obtain informed consent, confirm diagnosis, and measure baseline pre‑glucocorticoid serum androstenedione. After eligibility confirmation, the baseline visit initiates study treatment, followed by scheduled follow‑up visits at Weeks 4, 12, and 24 to assess safety, adherence, and hormone levels; the Week 24 visit includes the primary efficacy assessment (change from baseline in pre‑GC androstenedione). The end‑of‑study visit concludes the trial after approximately 24 weeks of participant involvement. Early termination may occur per protocol (e.g., withdrawal of consent or unacceptable safety).

The investigational product, identified as NBI-74788, contains the active substance crinecerfont and is supplied as an oral capsule. Each capsule is formulated to deliver a dose of 00 mg and is administered by mouth; the specific dosing frequency is defined in the study protocol.

Participants in this open‑label Phase 3b study continue their established glucocorticoid regimen at a stable dose for at least six months, serving as the background standard‑of‑care therapy. No placebo or additional comparator treatment is employed. Drug administration is performed under direct supervision, and adherence is monitored in accordance with protocol‑specified procedures.

Efficacy will be assessed by determining the change from baseline in pre‑glucocorticoid serum androstenedione levels at Week 24. The primary endpoint focuses on the reduction of this androgen marker in adults with classic congenital adrenal hyperplasia who are receiving a stable glucocorticoid regimen.

Serum samples will be collected prior to glucocorticoid dosing at screening (baseline) and at the Week 24 visit. The difference between the baseline value and the Week 24 value will be calculated for each participant, and the mean change across the study population will be analyzed to evaluate the effect of crinecerfont.