{"doi":"10.1210/clinem/dgab438","title":"Tildacerfont in Adults With Classic Congenital Adrenal Hyperplasia: Results from Two Phase 2 Studies","abstract":"CONTEXT: Congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is typically treated with lifelong supraphysiologic doses of glucocorticoids (GCs). Tildacerfont, a corticotropin-releasing factor type-1 receptor antagonist, may reduce excess androgen production, allowing for GC dose reduction. OBJECTIVE: Assess tildacerfont safety and efficacy. DESIGN AND SETTING: Two Phase 2 open-label studies. PATIENTS: Adults with 21OHD. INTERVENTION: Oral tildacerfont 200 to 1000 mg once daily (QD) (n = 10) or 100 to 200 mg twice daily (n = 9 and 7) for 2 weeks (Study 1), and 400 mg QD (n = 11) for 12 weeks (Study 2). MAIN OUTCOME MEASURE: Efficacy was evaluated by changes from baseline at 8 am in adrenocorticotropic hormone (ACTH), 17-hydroxyprogesterone (17-OHP), and androstenedione (A4) according to baseline A4 ≤ 2× upper limit of normal (ULN) or A4 > 2× ULN. Safety was evaluated using adverse events (AEs) and laboratory assessments. RESULTS: In Study 1, evaluable participants with baseline A4 > 2× ULN (n = 11; 19-67 years, 55% female) had reductions from baseline in ACTH (-59.4% to -28.4%), 17-OHP (-38.3% to 0.3%), and A4 (-24.2% to -18.1%), with no clear dose response. In Study 2, participants with baseline A4 > 2× ULN (n = 5; 26-63 years, 40% female) had ~80% maximum mean reductions in biomarker levels. ACTH and A4 were normalized for 60% and 40%, respectively. In both studies, participants with baseline A4 ≤ 2× ULN maintained biomarker levels. AEs (in 53.6% of patients overall) included headache (7.1%) and upper respiratory tract infection (7.1%). CONCLUSIONS: For patients with 21OHD, up to 12 weeks of oral tildacerfont reduced or maintained key hormone biomarkers toward normal.","journal":"The Journal of Clinical Endocrinology & Metabolism","year":2021,"id":159445,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":41,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.96,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":670469,"name":"Chris N. Barnes","orcid":"0000-0002-2237-4842","position":1,"is_corresponding":false},{"id":670470,"name":"Michael Huang","orcid":"0000-0001-6870-1688","position":2,"is_corresponding":false},{"id":382681,"name":"Erik A. Imel","orcid":"0000-0002-7284-3467","position":3,"is_corresponding":false},{"id":671453,"name":"Ivy-Joan Madu","orcid":null,"position":4,"is_corresponding":false},{"id":404052,"name":"Deborah P. Merke","orcid":"0000-0002-3746-0460","position":5,"is_corresponding":false},{"id":670471,"name":"D. J. W. Moriarty","orcid":"0000-0002-9360-5556","position":6,"is_corresponding":false},{"id":671454,"name":"Samer Nakhle","orcid":null,"position":7,"is_corresponding":false},{"id":670472,"name":"Ron S. Newfield","orcid":"0000-0001-6274-8530","position":8,"is_corresponding":false},{"id":670473,"name":"Maria G. Vogiatzi","orcid":"0000-0001-9523-0084","position":9,"is_corresponding":false},{"id":369854,"name":"Richard J. Auchus","orcid":"0000-0001-6815-6181","position":10,"is_corresponding":false},{"id":436044,"name":"Kyriakie Sarafoglou","orcid":"0000-0002-5741-3629","position":0,"is_corresponding":true}],"reference_count":25,"raw_metadata":null,"created_at":"2026-07-18T23:44:39.550981Z","pmid":"34146101","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":[]}