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，经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。脑下垂体中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，可能会允许较低的糖皮质激素治疗。该作用机制已在先前的概念验证研究中得到验证，并已在健康志愿者的第一阶段临床研究和CAH患者的第二阶段剂量发现研究中被证明是安全的。在第二阶段研究中，疾病控制水平在基线水平较差的患者的生物标志物减少；而疾病控制水平在基线水平良好的患者仅表现出微小的变化。 一项随机、双盲、安慰剂对照研究正在进行中，该研究将探索CRF 1型受体拮抗剂的安全性和有效性。本研究旨在探索一种治疗先天性肾上腺增生症的新方法。

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.