{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:52:34Z","timestamp":1791337954350,"version":"4.3.1"},"reference-count":24,"publisher":"The Endocrine Society","issue":"3","license":[{"start":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T00:00:00Z","timestamp":1634256000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Neurocrine Biosciences, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,2,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess androgen production. Corticotropin-releasing factor type 1 receptor (CRF1R) antagonism may decrease adrenal androgen production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This work aimed to evaluate the safety, tolerability, and efficacy of crinecerfont (NBI-74788), a selective CRF1R antagonist, in 21OHD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This open-label, phase 2 study, with sequential cohort design (NCT03525886), took place in 6 centers in the United States. Participants included men and women, aged 18 to 50 years, with 21OHD. Interventions included 4 crinecerfont regimens, each administered orally for 14 consecutive days: 50 or 100 mg once daily at bedtime (cohorts 1 and 2, respectively); 100 mg once daily in the evening (cohort 3); and 100 mg twice daily (cohort 4). Participants could enroll in more than 1 cohort. Main outcomes included changes from baseline to day 14 in adrenocorticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eighteen participants (11 women, 7 men) were enrolled: cohort 1 (n\u2005=\u20058), cohort 2 (n\u2005=\u20057), cohort 3 (n\u2005=\u20058), cohort 4 (n\u2005=\u20058). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (\u201366%), 17OHP (\u201364%), and androstenedione (\u201364%) with crinecerfont 100 mg twice a day. In female participants, 73% (8\/11) had a 50% or greater reduction in testosterone levels; male participants had median 26% to 65% decreases in androstenedione\/testosterone ratios.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Crinecerfont treatment for 14 days lowered ACTH and afforded clinically meaningful reductions of elevated 17OHP, androstenedione, testosterone (women), or androstenedione\/testosterone ratio (men) in adults with 21OHD. Longer-term studies are required to evaluate the effects of crinecerfont on clinical end points of disordered steroidogenesis and glucocorticoid exposure in patients with 21OHD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgab749","type":"journal-article","created":{"date-parts":[[2021,10,20]],"date-time":"2021-10-20T11:33:55Z","timestamp":1634729635000},"page":"801-812","source":"Crossref","is-referenced-by-count":53,"title":["Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia"],"prefix":"10.1210","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6815-6181","authenticated-orcid":false,"given":"Richard J","family":"Auchus","sequence":"first","affiliation":[{"name":"Departments of Pharmacology and Internal Medicine, Division of Metabolism, Endocrinology and Diabetes, University of Michigan Medical School, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5741-3629","authenticated-orcid":false,"given":"Kyriakie","family":"Sarafoglou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, University of Minnesota Medical School, Minneapolis, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia Y","family":"Fechner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Endocrinology, University of Washington School of Medicine, Seattle Children\u2019s Hospital, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria G","family":"Vogiatzi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Children\u2019s Hospital of Philadelphia , Philadelphia, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7284-3467","authenticated-orcid":false,"given":"Erik A","family":"Imel","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanlee M","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Endocrinology, University of Colorado School of Medicine, Aurora, Colorado, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagdeep","family":"Giri","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences Inc, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sturgeon","sequence":"additional","affiliation":[{"name":"Neurocrine Biosciences Inc, San Diego, California, 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