ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)
Baseline characteristics of adults with classic congenital adrenal hyperplasia enrolled in CAHtalyst, a phase 3 study of Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist
Richard Auchus 1 , Oksana Hamidi 2 , Rosario Pivonello 3 , Irina Bancos 4 , Selma Witchel 5 , Andrea Isidori 6 , Patrice Rodien 7,8 , Umasuthan Srirangalingam 9 , Florian Kiefer 10 , Henrik Falhammar 11 , Deborah Merke 12,13 , Nicole Reisch 14 , Julia Sturgeon 15 , Eiry Roberts 15 , Vivian Lin 15 , Jean L Chan 15 & Robert Farber 15
1University of Michigan Medical School, Ann Arbor, USA; 2University of Texas Southwestern Medical Center, Department of Internal Medicine, Dallas, USA; 3University of Naples Federico II, Napoli, Italy; 4Mayo Clinic, Rochester, USA; 5University of Pittsburgh School of Medicine, Pittsburgh, USA; 6Sapienza University of Rome, Roma, Italy; 7Mitovasc, Angers, France; 8Angers University Hospital Center, Angers, France; 9University of College London, London, UK; 10Medical University of Vienna, Wien, Austria; 11Karolinska Institute, Stockholm, Sweden; 12NIH Clinical Center, Bethesda, USA; 13Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, USA; 14Ludwig Maximilian University of Munich, München, Germany; 15Neurocrine Biosciences, San Diego, USA
Objectives: To describe the baseline characteristics of individuals enrolled in CAHtalyst (NCT04490915), a randomized, double-blind, placebo-controlled, Phase 3 study evaluating the safety and efficacy of crinecerfont (a corticotropin-releasing factor type 1 receptor [CRF1] antagonist) in adults with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD).
Methods: The study included adults (age ≥18 years) with classic 21OHD. Key eligibility criteria included glucocorticoid dose >13 mg/m2/day in hydrocortisone equivalents (HCe; conversion factors: 4× for predni[so]lone, 60× for dexamethasone) adjusted for body surface area (BSA) with stable dose for ≥1 month prior to screening, and normal or elevated androstenedione (A4). Baseline demographics and characteristics were summarized descriptively in all randomized participants.
Results: Of 182 enrolled participants, 51% were men and 90% were White. Mean (±S.D.) age was 30.8±9.9 years (range: 18–58 years), mean BSA was 1.8±0.2 m2, and mean body mass index (BMI) was 29.8±7.0 kg/m2 (with BMI ≥30 kg/m2 in 47% of participants). The mean total daily glucocorticoid dose was 17.6±4.9 mg/m2/day (32.3±9.3 mg/day) HCe, with 57% on hydrocortisone alone, 30% on a predniso(lo)ne-containing regimen, and 13% on a dexamethasone-containing regimen. In addition, 86% of participants were on fludrocortisone (mean dose: 136±72 μg/day). Mean (±S.D.) hormone concentrations prior to the morning glucocorticoid dose were as follows: adrenocorticotropic hormone, 264±317 pg/ml; 17-hydroxyprogesterone, 9467±8829 ng/dl; A4, 620±729 ng/dl; testosterone (T) in females, 86±85 ng/dl; A4/T in males, 2.2±2.4; follicle-stimulating hormone in males, 6.3±9.4 IU/l; and luteinizing hormone in males, 4.6±5.0 IU/l. Among the 90 females, 42 (47%) reported a history of hirsutism; of the 66 females of childbearing potential not on hormonal or intrauterine contraception, 35 (53%) reported a history of amenorrhea or menstrual irregularities. Among the 92 males, 44 (48%) reported a history of testicular adrenal rest tumors (TARTs) while 53 (58%) had evidence of TARTs by ultrasound prior to study entry. Comorbidities included osteopenia (15%), hypertension (10%), osteoporosis (5%), and diabetes mellitus (2%).
Conclusion: In a Phase 3 trial evaluating crinecerfont (a CRF1 antagonist) in adults with classic 21OHD, clinical evidence of glucocorticoid and androgen excess (e.g., high prevalence of obesity, hirsutism [females], and TARTs [males]) were observed at baseline. Androgens and other steroid biomarkers were elevated despite treatment with supraphysiological doses of glucocorticoids. These findings emphasize the urgent need for novel glucocorticoid-sparing treatments for this chronic condition.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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