ECEESPE2025 Rapid Communications Rapid Communications 13: Adrenal and Cardiovascular Endocrinology Part 2 (6 abstracts)
Crinecerfont enables glucocorticoid dose reductions while maintaining/improving androstenedione in paediatric patients with congenital adrenal hyperplasia: subgroup analyses from CAHtalyst™ paediatric
Oksana Lekarev 1 , Ayca Erkin-Cakmak 2 , Maria Vogiatzi 3 , Erik Imel 4 , Maria Clemente 5 , Régis Coutant 6 , Thom Board 7 , Gelliza Rosales 7 , Eiry Roberts 7 , George Jeha 7 , Robert Farber 7 & Jean Chan 7
1Weill Cornell Medical College and NewYork-Presbyterian Hospital, New York, United States; 2University of California San Francisco, San Francisco, United States; 3Children’s Hospital of Philadelphia, Philadelphia, United States; 4Indiana University School of Medicine, Indianapolis, United States; 5University Hospital Vall d’Hebron and Biomedical Research Networking Center on Rare Diseases (CIBERER), Barcelona, Spain; 6CHU d’Angers, Pediatric Endocrinology Unit, Angers, France; 7Neurocrine Biosciences, Inc., San Diego, United States
JOINT3270
Background: Crinecerfont, a corticotropin releasing factor type 1 receptor antagonist, is a first-in-class medication that is FDA-approved for adjunctive treatment to glucocorticoid (GC) replacement to control androgens in patients with classic congenital adrenal hyperplasia (CAH). In phase 3 trials, crinecerfont significantly reduced excess androgens, enabling subsequent GC dose reductions in paediatric and adult patients with CAH.
Objective: To analyse changes in androstenedione (A4) levels and GC dose reductions while maintaining/improving A4 in subgroups of participants from CAHtalyst™ Paediatric (NCT04806451).
Methods: Participants were randomised 2:1 to double-blind treatment with crinecerfont (25, 50, or 100 mg BID based on weight) or placebo for 28 weeks. GC doses were kept stable for 4 weeks to evaluate the impact on androgens and then reduced to a target of 8-10 mg/m2/d in hydrocortisone equivalents (HCe) by Week 28 while maintaining/improving A4 relative to baseline (BL). Least squares (LS) mean changes from BL in A4 (before morning GC dose) at Week 4 and in GC dose at Week 28 were analysed in the overall population and in subgroups defined by: region (US, outside US); sex (male, female); race (white, non-white); age (<12, 12-17 years); weight (<55, ≥55 kg); body mass index (BMI) (<85th, ≥85th percentile); pubertal stage (Tanner 1-2, 3-5); BL A4 (≤ULN [upper limit of normal], >ULN); and BL GC dose (<16, ≥16 mg/m2/d HCe, for GC change only).
Results: Among 103 participants (crinecerfont=69, placebo=34), mean age (±SD) was 12.1±3.5 years; 51% were male. Mean A4 at BL was 15.0±16.1 nmol/l; mean GC dose was 16.4±3.9 mg/m2/d. At Week 4, A4 was significantly reduced with crinecerfont but increased with placebo (-6.9 vs. +2.5 nmol/l; LS mean difference [LSMD]: -9.3 nmol/l; P=0.0002). LSMDs of the point estimates for A4 change at Week 4 favoured crinecerfont in all subgroups. At Week 28, GC dose was significantly reduced with crinecerfont (while maintaining or improving A4) but increased with placebo (-18.0% vs. +5.6%; LSMD: -23.5%; P <0.0001). LSMDs of the point estimates for percent change in GC dose at Week 28 favoured crinecerfont in all subgroups. All subgroup results were consistent with the overall population.
Conclusion: Crinecerfont enabled GC dose reductions while maintaining/improving A4 in paediatric patients with CAH across multiple subgroups. These results demonstrate that paediatric patients with CAH can derive the androgen-lowering and GC-lowering benefits of crinecerfont regardless of region, sex, race, age, weight/BMI, pubertal stage, or pretreatment A4 level or GC dose.
Volume 110
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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