Baseline characteristics of children and adolescents with classic congenital adrenal hyperplasia enrolled in CAHtalyst pediatric, a phase 3 Study of Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist

Kyriakie Sarafoglou; Mimi Kim; Maya Lodish; Eric Felner; Laetitia Martinerie; Natalie J. Nokoff; Maria Clemente; Patricia Y. Fechner; Maria Vogiatzi; Phyllis Speiser; Julia Sturgeon; Eiry Roberts; George Jeha; Jean L. Chan; Robert Farber

doi:10.1530/endoabs.99.P225

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Endocrine Abstracts (2024) 99 P225 | DOI: 10.1530/endoabs.99.P225

ECE2024 Poster Presentations Adrenal and Cardiovascular Endocrinology (95 abstracts)

Baseline characteristics of children and adolescents with classic congenital adrenal hyperplasia enrolled in CAHtalyst pediatric, a phase 3 Study of Crinecerfont, a corticotropin-releasing factor type 1 receptor antagonist

Kyriakie Sarafoglou ¹ , Mimi Kim ^2,3 , Maya Lodish ⁴ , Eric Felner ^5,6 , Laetitia Martinerie ⁷ , Natalie J. Nokoff ⁸ , Maria Clemente ⁹ , Patricia Y. Fechner ¹⁰ , Maria Vogiatzi ¹¹ , Phyllis Speiser ^12,13 , Julia Sturgeon ¹⁴ , Eiry Roberts ¹⁴ , George Jeha ¹⁴ , Jean L. Chan ¹⁴ & Robert Farber ¹⁴

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Author affiliations

¹University of Minnesota Medical School, Minneapolis, USA; ²Children’s Hospital Los Angeles, Los Angeles, USA; ³Keck School of Medicine of USC, Los Angeles, USA; ⁴UCSF Benioff Children’s Hospital - San Francisco, San Francisco, USA; ⁵Emory University School of Medicine, Atlanta, USA; ⁶Children’s Healthcare of Atlanta, Atlanta, USA; ⁷Hospital Robert Debré Ap-Hp, Paris, France; ⁸Children’s Hospital Colorado Anschutz Medical Campus, Aurora, Aurora, USA; ⁹Vall d’Hebron University Hospital, Barcelona, Spain; ¹⁰Seattle Children’s Hospital, Seattle, USA; ¹¹The Children’s Hospital of Philadelphia, Philadelphia, USA; ¹²Cohen Children’s Medical Center, New Hyde Park, USA; ¹³Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, USA; ¹⁴Neurocrine Biosciences Inc., San Diego, USA

Objective: To describe the baseline characteristics of individuals enrolled in CAHtalyst Pediatric (NCT04806451), 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 children and adolescents with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OHD CAH).

Methods: Key eligibility criteria included: male or female, age 2-17 years; glucocorticoid (GC) dose >12 mg/m²/day in hydrocortisone equivalents (HCe) adjusted for body surface area (BSA), on a stable dose for ≥1 month prior to screening; androstenedione (A4) greater than midpoint of reference range; and 17-hydroxyprogesterone (17-OHP) >2× upper limit of normal prior to morning GC dose. Baseline demographics and characteristics were summarized descriptively in all randomized participants.

Results: Of 103 enrolled participants at 46 study centers, 52% were male and 63% were White. Mean (±S.D.) age was 12±3 years (range: 4–17), with 54% ages 12–17 years. Overall, 58% were overweight/obese (body mass index [BMI] ≥85th percentile), BMI standard deviation score (SDS) was 1.2±0.9, height SDS was 0.3±1.3, and mean BSA was 1.5±0.3 m². Tanner stages (breast or testicular volume) were as follows: 1 (29%), 2 (12%), 3 (13%), 4 (18%), and 5 (28%). Mean (±S.D.) total daily GC dose was 16.4±3.9 mg/m²/day HCe, with 92% on hydrocortisone and 8% on a predniso(lo)ne-containing regimen. 87% were taking fludrocortisone (mean dose: 1.1±0.5 mg/day), with 10% on GnRH agonists and 3% on aromatase inhibitors. Mean (±S.D.) hormone concentrations prior to morning GC dose were: ACTH, 329±344 pg/ml; 17-OHP, 8682±6847 ng/dl; A4, 431±461 ng/dl; testosterone (T) in females, 73±67 ng/dl; and A4/T in males, 3.5±7.6. Comorbidities included advanced bone age by ≥1 year (62%), early puberty (33%), irregular menstrual cycles (12% females), hirsutism (12% females), and testicular adrenal rest tumors (6% males). The mean ratio of bone age to chronological age was highest in males at Tanner stage 1 (1.4±0.4) and in females at Tanner stage 2 (1.2±0.2).

Conclusion: In a Phase 3 trial evaluating crinecerfont in children and adolescents with 21-OHD CAH on GC doses >12 mg/m²/day HCe, there was clinical evidence of GC and androgen excess (e.g., overweight/obesity, advanced bone age, and early puberty). Androgen levels were elevated despite treatment with GC doses >12 mg/m²/day HCe, highlighting the need for novel treatments for this condition.