The New England Journal of MedicinePhase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia

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A recent phase 3 trial evaluated the efficacy of crinecerfont, an oral corticotropin-releasing factor type 1 receptor antagonist, in pediatric patients with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The study aimed to assess the drug’s ability to reduce androstenedione levels and allow for a decrease in glucocorticoid dosage while maintaining hormonal control.

Study Design:

• Multinational, randomized, placebo-controlled trial
• 103 pediatric participants with CAH
• 2:1 ratio assignment to crinecerfont or placebo for 28 weeks
• Glucocorticoid dose maintained for 4 weeks, then adjusted to target 8.0-10.0 mg/m²/day (hydrocortisone equivalents)
• Primary endpoint: Change in androstenedione level from baseline to week 4
• Key secondary endpoint: Percent change in glucocorticoid dose from baseline to week 28 while maintaining androstenedione control

Key Findings:

• At week 4, androstenedione levels decreased by 197 ng/dL in the crinecerfont group vs. increased by 71 ng/dL in the placebo group (LSMD: -268 ng/dL; P<0.001)
• Mean androstenedione values at week 4: 208 ng/dL (crinecerfont) vs. 545 ng/dL (placebo)
• At week 28, glucocorticoid dose decreased by 18.0% with crinecerfont vs. increased by 5.6% with placebo (LSMD: -23.5 percentage points; P<0.001)
• Most common adverse events: headache, pyrexia, and vomiting

HCN Medical Memo
Although these results are promising, long-term studies are needed to assess the safety and efficacy of crinecerfont in pediatric CAH patients. Physicians should consider the potential benefits of reduced glucocorticoid exposure when evaluating future treatment options for children with CAH.

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