Phase 2 Multi-center Study of ATR-101 for the Treatment of Congenital Adrenal Hyperplasia

ATR-101治疗先天性肾上腺增生症的2期多中心研究

• 批准号: 10252568
• 负责人: Deborah Merke
• 金额: --
• 依托单位: CLINICAL CENTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10252568
• 关键词: 21-hydroxylase deficiency; Adrenal Cortex Diseases; Adrenal Glands; Adult; Adverse event; Aldosterone; Androgens; Birth; Child Development; Cholesterol; Cholesterol Esters; Cholesterol Homeostasis; Clinical; Congenital adrenal hyperplasia; Corticotropin; Cushing Syndrome; Development; Dose; Enrollment; Enzymes; Esterification; Glucocorticoids; Growth and Development function; Hormones; Hydrocortisone; Hydroxyprogesterone; Hyperandrogenism; Iatrogenesis; Infertility; Lead; Longevity; Metabolic syndrome; Multicenter Studies; Oral; Outcome Measure; Pathway interactions; Patients; Phase; Physiological; Placebos; Risk; Safety; Serious Adverse Event; Single-Blind Study; Steroid biosynthesis; Steroids; Therapeutic Agents; experience; prevent; primary outcome; screening; side effect; sterol O-acyltransferase 1; trend

This was a multicenter, single-blind, multiple dose study of Nevanimibe (ATR- 101) with a placebo washout component. The Screening Period was followed by a placebo, baseline lead-in period. Subjects then received the lowest dose of Nevanimibe for 14 days followed by a single-blind placebo Washout Period of 14 days. Safety and efficacy assessments occurred at the end of treatment and following the washout period. If the primary outcome measure (17-OHP 2x ULN) was not achieved, the subject proceeded to the next higher dose level. A total of 5 ATR-101 dose levels were possible. Ten patients were enrolled; nine completed the study, and 1 discontinued early due to a related serious adverse event. Two subjects met the primary endpoin, and 5 others experienced 17-hydroxyprogesterone decreases ranging from 27% to 72% during treatment. the most common side effects were gastointestinal (30%). There were no dose-related trends in adverse events. Nevanimibe (ATR-101) decreased 17-hydroxyprogesterone levels within 2 weeks of treatment. Larger studies of longer duration are needed to further evaluate its efficacy as add-on therapy for CAH.

这是一项 Nevanimibe (ATR-101) 与安慰剂洗脱成分的多中心、单盲、多剂量研究。筛选期之后是安慰剂、基线导入期。然后受试者接受 14 天最低剂量的 Nevanimibe，随后进行 14 天的单盲安慰剂清除期。安全性和有效性评估在治疗结束时和清除期后进行。如果未达到主要结果指标（17-OHP 2x ULN），受试者将继续接受下一个更高的剂量水平。 ATR-101 总共有 5 种剂量水平。招募了 10 名患者； 9 名完成了研究，1 名由于相关的严重不良事件而提前终止。两名受试者达到了主要终点，另外 5 名受试者在治疗期间 17-羟基孕酮下降了 27% 至 72%。 最常见的副作用是胃肠道反应（30%）。 不良事件没有剂量相关趋势。 Nevanimibe (ATR-101) 在治疗 2 周内降低 17-羟基孕酮水平。 需要进行更大规模、持续时间更长的研究来进一步评估其作为 CAH 附加疗法的疗效。