Crinecerfont, a CRF1 Receptor Antagonist, Lowers Adrenal Androgens in Adolescents With Congenital Adrenal Hyperplasia

Ron S. Newfield, Kyriakie Sarafoglou, Patricia Y. Fechner, Natalie J. Nokoff, Richard J. Auchus, Maria G. Vogiatzi, George S. Jeha, Nagdeep Giri, Eiry Roberts, Julia Sturgeon, Jean L. Chan, Robert H. Farber

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Context: Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist, has been shown to reduce elevated adrenal androgens and precursors in adults with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD), a rare autosomal recessive disorder characterized by cortisol deficiency and androgen excess due to elevated adrenocorticotropin. Objective: To evaluate the safety, tolerability, and efficacy of crinecerfont in adolescents with 21OHD CAH. Methods: This was an open-label, phase 2 study (NCT04045145) at 4 centers in the United States. Participants were males and females, 14 to 17 years of age, with classic 21OHD CAH. Crinecerfont was administered orally (50 mg twice daily) for 14 consecutive days with morning and evening meals. The main outcomes were change from baseline to day 14 in circulating concentrations of ACTH, 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results: 8 participants (3 males, 5 females) were enrolled; median age was 15 years and 88% were Caucasian/White. After 14 days of crinecerfont, median percent reductions from baseline to day 14 were as follows: ACTH, −57%; 17OHP, −69%; and androstenedione, −58%. In female participants, 60% (3/5) had ≥50% reduction from baseline in testosterone. Conclusion: Adolescents with classic 21OHD CAH had substantial reductions in adrenal androgens and androgen precursors after 14 days of oral crinecerfont administration. These results are consistent with a study of crinecerfont in adults with classic 21OHD CAH.

Original languageEnglish (US)
Pages (from-to)2871-2878
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume108
Issue number11
DOIs
StatePublished - Nov 1 2023

Bibliographical note

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.

Keywords

  • 21-hydroxylase deficiency
  • CRF type 1 receptor antagonist
  • adolescents
  • congenital adrenal hyperplasia
  • crinecerfont
  • pediatric

PubMed: MeSH publication types

  • Journal Article

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