A Phase 2/3 Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of Atumelnant Treatment in Pediatric Participants With Congenital Adrenal Hyperplasia Including a Long-Term Extension
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 153
- 试验地点
- 50
- 主要终点
- Change from baseline in morning serum androstenedione (A4) (Part A)
研究概览
简要总结
The purpose of this study is to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of atumelnant treatment in pediatric participants with classic congenital adrenal hyperplasia (CAH).
详细描述
This Phase 2/3 plus open-label extension study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of atumelnant treatment in pediatric participants with classic CAH. Part A is a Phase 2, open-label, semi-sequential cohorts portion of the study. Part B is the Phase 3, double-blind, randomized, placebo controlled confirmatory portion of the study. Part C is the open-label extension (OLE) portion of the study. Participants in Part A and B are eligible to enroll in Part C (OLE).
A total of approximately 153 participants may be enrolled in the study (planned and optional cohorts) ages 1 to < 18 years old.
The first 3 cohorts in Part A are for ages 12 to <18 years and will be semi-sequential, and Safety Review Committee (SRC) review of data and approval to proceed is required prior to enrolling each subsequent cohort. The fourth cohort in Part A is for ages 1 to 11 years old and will begin after Cohorts 1 and 2 have been completed, additional requirements are fulfilled, and following SRC review of Cohorts 1 and 2 data.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A and B participants are eligible to be included in the study only if all of the following criteria apply:
- •Male or female at birth, between 1 to <18 years of chronological age at the time of signing the Informed Consent Form (ICF).
- •Have a medically confirmed diagnosis of classic CAH due to 21-hydroxylase deficiency (21-OHD) based on standard medically accepted criteria such as elevated 17-OHP level, confirmed CYP21A2 genetic testing, positive newborn screening with confirmatory second tier testing, or cosyntropin stimulation.
- •Participants must have an elevated morning serum A4 level >ULN during Screening obtained prior to morning glucocorticoid (GC) administration.
- •Participants must be on a stable supraphysiologic GC replacement therapy for at least one month prior to Screening.
- •Compliance, as judged per Investigator discretion, with GC replacement and mineralocorticoid replacement (if applicable) regimen documented during the Screening Period.
- •Biochemical euthyroidism as determined by the Investigator.
- •Part C inclusion criteria require participants to complete treatment in either Part A or Part B and in the Investigator's opinion it would benefit the participant to continue in Part C, regardless of age.
排除标准
- •Part A and Part B: Individuals in Part A and Part B who meet any of the following criteria will be excluded from participation in this study:
- •Diagnosis of any form of CAH other than classic 21-OHD.
- •Participants treated with other GCs within 30 days of Screening.
- •Stress dose of GC therapy within 2 weeks of start of Screening, defined as any dose above the normal maintenance dose, including but not limited to intravenous (IV) or intramuscular (IM) hydrocortisone.
- •Use of growth hormones within 1 week of start of Screening for short acting, or within 6 weeks of start of Screening for long acting.
- •Use of a corticotropin-releasing factor receptor antagonist within 14 days of Screening.
- •History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
- •Abnormal sleep/wake cycles (as determined by the Investigator).
- •Female participants who are pregnant or lactating.
- •Participants who have been dosed with an investigational drug (including atumelnant) in any prior clinical study within 60 days or 5 half-lives (whichever is longer) prior to the first dose.
- •Individuals in Part C who do not meet the Part C Inclusion Criteria.
研究组 & 干预措施
Treatment (Part A)
Open-label, semi-sequential cohorts.
干预措施: Atumelnant (Drug)
Active Treatment (Part B)
Randomized, Parallel Arms, Double-Blind
干预措施: Atumelnant (Drug)
Placebo (Part B)
Randomized, Parallel Arms, Double-Blind
干预措施: Placebo (Drug)
Open-Label Treatment (Part C)
Open-label treatment period for participants entering Part C from Part A and B.
干预措施: Atumelnant (Drug)
结局指标
主要结局
Change from baseline in morning serum androstenedione (A4) (Part A)
时间窗: Week 8
Percent change from baseline in glucocorticoid (GC) daily dose while serum early morning A4 ≤Upper Limit of Normal (ULN) (Part B)
时间窗: Week 28
Change from baseline in serum early morning A4 over time (Part C)
时间窗: Up to Week 260
次要结局
- Change from baseline in morning serum 17-hydroxyprogesterone (17-OHP) (Part A)(Week 8)
- Plasma and/or blood concentrations of atumelnant (Part A)(Up to Week 8)
- Change from baseline in serum early morning A4 (Part B)(Week 4)
- Change from baseline in serum early morning 17-OHP (Part B)(Week 4)
- Proportion of participants with physiologic GC dose while serum early morning A4 <ULN (Part B)(Week 28)
- Change from baseline in serum early morning 17-OHP over time (Part C)(Up to Week 260)
- Percent change from baseline in GC daily dose over time (Part C)(Up to Week 260)
- Proportion of participants with physiologic GC dose while serum early morning A4 <ULN over time (Part C)(Up to Week 260)