{"doi":"10.1210/clinem/dgab749","title":"Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia","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 = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (–66%), 17OHP (–64%), and androstenedione (–64%) 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>","journal":"The Journal of Clinical Endocrinology &amp; Metabolism","year":2022,"id":650628,"datarank":0.5983476069846413,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"self_citation_contribution":0.5983476069846413,"citation_network_contribution":0.0,"self_endowment_contribution":0.5983476069846413,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":53,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":436044,"name":"Kyriakie Sarafoglou","orcid":"0000-0002-5741-3629","position":1,"is_corresponding":false},{"id":1696512,"name":"Patricia Y Fechner","orcid":null,"position":2,"is_corresponding":false},{"id":1696513,"name":"Maria G Vogiatzi","orcid":null,"position":3,"is_corresponding":false},{"id":382681,"name":"Erik A. Imel","orcid":"0000-0002-7284-3467","position":4,"is_corresponding":false},{"id":1696514,"name":"Shanlee M Davis","orcid":null,"position":5,"is_corresponding":false},{"id":1696515,"name":"Nagdeep Giri","orcid":null,"position":6,"is_corresponding":false},{"id":1205016,"name":"Julia Sturgeon","orcid":null,"position":7,"is_corresponding":false},{"id":1205017,"name":"Eiry Roberts","orcid":null,"position":8,"is_corresponding":false},{"id":1696516,"name":"Jean L Chan","orcid":null,"position":9,"is_corresponding":false},{"id":1696517,"name":"Robert H Farber","orcid":null,"position":10,"is_corresponding":false},{"id":369854,"name":"Richard J. Auchus","orcid":"0000-0001-6815-6181","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Crinecerfont Lowers Elevated Hormone Markers in Adults With 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia","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 = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (–66%), 17OHP (–64%), and androstenedione (–64%) 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>","is_dataset_classified":null,"base_score":3.9889840465642745,"endowment":3.9889840465642745,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34653252","pmcid":"PMC8851935","openalex_id":"https://openalex.org/W3206029402","authors":[],"funders":[{"funder_name":"Neurocrine Biosciences, Inc.","grant_id":"","title":null}],"total_grants":1,"fwci":2.2214,"citation_percentile":0.89200966,"influential_citations":0,"citation_trend":[{"year":2021,"count":2},{"year":2022,"count":8},{"year":2023,"count":9},{"year":2024,"count":11},{"year":2025,"count":14},{"year":2026,"count":9}],"oa_status":"green","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","oa_locations":[{"url":"https://scholarworks.indianapolis.iu.edu/bitstreams/0fa1647f-4be1-4872-b01d-9974a49ed93e/download","host_type":"repository"},{"url":"https://scholarworks.indianapolis.iu.edu/bitstreams/0fa1647f-4be1-4872-b01d-9974a49ed93e/download","host_type":"repository"},{"url":"http://academic.oup.com/jcem/advance-article-pdf/doi/10.1210/clinem/dgab749/41025761/dgab749.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/jcem/article-pdf/107/3/801/42544562/dgab749.pdf","host_type":"publisher"},{"url":"https://hdl.handle.net/1805/32961","host_type":"repository"},{"url":"https://doi.org/10.1210/clinem/dgab749","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34653252","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8851935","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8851935","host_type":"Europe_PMC"}],"fields_of_study":["Sexual Differentiation and Disorders","Hormonal and reproductive studies","Adrenal Hormones and Disorders","Adolescent","Adult","Female","Humans","Male","Middle Aged","Young Adult","17-alpha-Hydroxyprogesterone","Administration, Oral","Adrenal Hyperplasia, Congenital","Adrenocorticotropic Hormone","Androstenedione","Azabicyclo Compounds","Biomarkers","Dose-Response Relationship, Drug","Oxadiazoles","Receptors, Corticotropin-Releasing Hormone","Testosterone","Treatment Outcome","CRF Receptor, Type 1","Amines","Thiazoles","Congenital adrenal hyperplasia due to 21 hydroxylase deficiency"],"mesh_terms":["CRF Receptor, Type 1","Administration, Oral","Adolescent","Adrenal Hyperplasia, Congenital","Adrenocorticotropic Hormone","Adult","Amines","Androstenedione","Dose-Response Relationship, Drug","Female","Humans","Male","Middle Aged","Oxadiazoles","Testosterone","Thiazoles","Biomarkers","Treatment Outcome","Receptors, Corticotropin-Releasing Hormone","17-alpha-Hydroxyprogesterone","Azabicyclo Compounds","Young Adult"],"keywords":["Androstenedione","Internal medicine","Medicine","Testosterone (patch)","Congenital adrenal hyperplasia","Endocrinology","Cohort","Tolerability","Androgen","Bedtime","Hormone","Adverse effect","21-Hydroxylase Deficiency","17-Hydroxyprogesterone","Nbi-74788","Crinecerfont"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"nct"},{"name":"doi"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-10T05:50:50.232159Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}