Modified-release Hydrocortisone Therapy as a Treatment for CAH

完成了一项为期6个月、随机、3期、在122名患有典型CAH的成人中进行的研究，比较了新开发的氢化可的松（MR-HC）缓释制剂与标准糖皮质激素。 这种新开发的氢化可的松制剂（Chronocort）旨在模拟正常的皮质醇昼夜节律。在NIH先前的一项II期研究中，与基线时的常规治疗相比，6个月时的MR-HC显示全天雄激素水平改善，并且这种雄激素降低是通过较低或相似的平均每日糖皮质激素剂量实现的。这导致了为期6个月的随机（MR-HC与标准糖皮质激素）国际多中心III期临床试验，这是CAH患者糖皮质激素治疗的第一个随机对照试验。3期研究在6个月时失败了主要结局，这是基于24小时激素谱。然而，有证据表明，与标准糖皮质激素治疗相比，在0700 h-1500 h之间对MR-HC进行更好的生化控制，早晨激素控制对于控制肾上腺雄激素的过夜增加很重要。 一项扩展研究正在进行中，患者报告的益处包括月经恢复以及患者和伴侣怀孕。这种新的氢化可的松制剂代表了CAH患者潜在的新治疗方法

A 6-month, randomized, Phase 3, study in 122 adults with classic CAH, comparing a newly-developed modified-release formulation of hydrocortisone (MR-HC) with standard glucocorticoid, was completed. This newly developed formulation of hydrocortisone (Chronocort) was designed to mimic the normal cortisol circadian rhythm. In a prior Phase 2 study at the NIH, compared to conventional therapy at baseline, MR-HC at 6 months showed improved androgen levels throughout the day and this lowering of androgens was achieved with a lower or similar average daily glucocorticoid dose. This led to the 6-month randomized (MR-HC vs. standard glucocorticoid) international multi-center phase 3 clinical trial, which is the first randomized, controlled trial of glucocorticoid treatment in patients with CAH. The Phase 3 study failed its primary outcome at 6 months, which was based on 24-hour hormone profiles. However, there was evidence of better biochemical control on MR-HC between 0700h-1500h compared to standard glucocorticoid therapy, and morning hormonal control is important in controlling the overnight increase in adrenal androgens. An extension study is underway with patient-reported benefits including menses restoration and patient and partner pregnancies. This novel hydrocortisone formulation represents a potential new treatment approach for patients with CAH