BSPED2024 Oral Communications Endocrine Oral Communications 1 (9 abstracts)
Crinecerfont in children and adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency: results from the phase 3 CAHtalyst pediatric study
Kyriakie Sarafoglou 1 , Mimi S. Kim 2 , Maya Lodish 3 , Eric I. Felner 4 , Laetitia Martinerie 5 , Natalie Nokoff 6 , Maria Clemente 7 , Patricia Y. Fechner 8 , Maria G. Vogiatzi 9 , Phyllis W. Speiser 10,11 , Mehul Dattani 12 , Gelliza B.G. Rosales 13 , Eiry Roberts 13 , George S. Jeha 13 , Robert Farber 13 & Jean L. Chan 13
1University of Minnesota Medical School and College of Pharmacy, Minneapolis, USA; 2Children’s Hospital Los Angeles and Keck School of Medicine of USC, Los Angeles, USA; 3University of California San Francisco, Benioff Children’s Hospital, San Francisco, USA; 4Emory University School of Medicine and Children’s Healthcare of Atlanta (CHOA), Atlanta, USA; 5Hôpital Universitaire Robert Debré, AP-HP, Université Paris Cité, Paris, France; 6University of Colorado School of Medicine, Children’s Hospital Colorado, Aurora, USA; 7University Hospital Vall d’Hebrón, Barcelona, Spain; 8University of Washington School of Medicine, Seattle Children’s Hospital, Seattle, USA; 9The Children’s Hospital of Philadelphia, Philadelphia, USA; 10Cohen Children’s Medical Center of NY, New Hyde Park, USA; 11Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, USA; 12Hospital for Children and University College London Hospital, London, United Kingdom; 13Neurocrine Biosciences Inc., San Diego, USA
Background: In phase 2 studies, crinecerfont reduced ACTH and adrenal androgens in adults and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH). CAHtalyst Pediatric (NCT04806451, EudraCT 2020-004381-19) is the largest interventional trial to date in pediatric patients with classic CAH.
Methods: Male and female participants, aged 2-17 years with elevated androstenedione and 17-OHP and taking GC at doses >12 mg/m2/d (hydrocortisone equivalent), were randomized (2:1) to twice-daily crinecerfont (25, 50, or 100 mg, based on weight) or placebo for 28 weeks. GC doses were maintained stable for 4 weeks and then reduced to a target dose of 8-10 mg/m2/d by Week 28 provided that androstenedione was controlled (≤120% of the baseline level or ≤upper limit of normal).
Results: Among 103 randomized participants (69 crinecerfont, 34 placebo), 53 were male, mean age was 12.1 years (range, 4-17), and >95% reached Week 28. Mean androstenedione (pre-morning GC dose) decreased from baseline to Week 4 with crinecerfont (14.1 to 7.3 nmol/l) but increased with placebo (16.9 to 19.0 nmol/l). The least-squares mean difference (LSMD) for androstenedione change from baseline was -9.3 nmol/l (P=0.0002; primary endpoint). 17-OHP decreased from baseline to Week 4 with crinecerfont (258 to 84 nmol/l) but not placebo (273 to 285 nmol/l), with an LSMD of -195 nmol/l (P<0.0001; key secondary endpoint). At baseline, mean GC doses were similar between the crinecerfont and placebo groups (16.5 and 16.3 mg/m2/d). At Week 28, GC dose was lower with crinecerfont than placebo (12.8 and 17.0 mg/m2/d), and the LSMD for GC percent change from baseline was -23.5% (P<0.0001; key secondary endpoint). Headache, pyrexia, and vomiting were the most common adverse events.
Conclusions: In pediatric patients with classic CAH, crinecerfont significantly decreased androstenedione and 17-OHP during a 4-week GC-stable period, enabling subsequent reduction in GC dosing while maintaining androstenedione control.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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