Study of a corticotropin releasing factor-1 receptor antagonist for the treatment of congenital adrenal hyperplasia

在先天性肾上腺增生症中，通常需要过量的糖皮质激素治疗来控制肾上腺雄激素的过量产生。垂体中CRF 1型受体的高亲和力和选择性小分子拮抗剂正在开发中，可能允许低糖皮质激素治疗。该药物的作用机制已在之前的概念验证研究中得到验证，并在健康志愿者的1期临床研究和CAH患者的2期剂量发现研究中被证明是安全的。在2期研究中，基线时疾病控制较差的患者生物标志物降低；而在基线时疾病控制良好的患者只有轻微的变化。

Excess glucocorticoid therapy is often needed to control the overproduction of adrenal androgens in congenital adrenal hyperplasia. High-affinity and selective small-molecule antagonists of CRF type 1 receptors in the pituitary gland are in development and might allow for lower glucocorticoid therapy. The mechanism of action has been validated in a previous proof-of-concept study and has been shown to be safe in Phase 1 clinical studies in healthy volunteers and Phase 2 dose finding studies of patients with CAH. In Phase 2 studies, patients with poor disease control at baseline had reductions in biomarkers; while patients with good disease control at baseline showed only minor changes. A randomized, double-blind, placebo-controlled study is underway which will explore the safety and efficacy of CRF type 1 receptor antagonist. This study represents the investigation of a novel therapy in the treatment of congenital adrenal hyperplasia.