A Randomized, Double-Blind, Multicenter, Placebo-Controlled Study to Evaluate the Safety and Efficacy of Atumelnant in Adult Participants With Classic Congenital Adrenal Hyperplasia (Calm-CAH)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 68
- 主要终点
- Proportion of participants with morning post-GC A4 ≤ ULN who are on physiologic GC replacement.
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety, PK, and PD of atumelnant in adults with classic CAH due to 21-OHD.
详细描述
This is a Phase 3, global, multicenter, randomized, double-blind, placebo-controlled study in adult participants (male or female age ≥18 to <75 years) with classic CAH due to 21-OHD who have been on a stable regimen of GCs for at least 2 months to evaluate efficacy, safety, PK, and PD of atumelnant administered once per day. Following a 3- to 6-week Screening Period, eligible participants will enter the Treatment Period where they will be randomly assigned in a 2:1 ratio to receive either atumelnant 80 mg once daily (with an option for dose escalation to 120 mg once daily at Week 20) or placebo.
A total of approximately 150 participants may be enrolled in the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 74 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, between ≥18 to <75 years of age at the time of signing the ICF.
- •Willing and able to understand and adhere to the study procedures as specified in the protocol and comply with the study treatment.
- •Have classic CAH due to 21-OHD confirmed by the Investigator.
- •Participants with Visit 2 levels of morning serum A4 as follows:
- •A4 >ULN and treated with <11 mg/m2/day (physiologic) GC doses
- •OR normal A4 (>0.5xULN to ≤1xULN) and treated with ≥14 mg/m2/day GC doses
- •OR A4 >ULN and treated with ≥11 mg/m2/day GC doses.
- •On a stable (defined as no dose change of >5 mg/day hydrocortisone equivalent within 2 months prior to Screening) regimen of GC replacement (e.g., hydrocortisone, prednisolone, prednisone, methylprednisolone, meprednisone, dexamethasone, cortisone acetate) at the time of informed consent.
- •If treated with mineralocorticoids (fludrocortisone), the dose should be stable for at least 1 month prior to Screening without orthostatic hypotension, and with serum sodium and potassium in the normal range.
- •If on estrogen therapy (any route), the dose must be stable for at least 3 months prior to Screening.
排除标准
- •Diagnosis of any form of CAH other than classic 21-OHD.
- •History of bilateral adrenalectomy, hypopituitarism, or other condition requiring chronic GC therapy.
- •Clinically significant medical condition or abnormal laboratory tests, as judged by the Investigator, other than CAH.
- •Concomitant mental condition rendering him/her unable to understand the nature, scope, and possible consequences of the study, and/or evidence of poor compliance with medical instructions.
- •History of cancer excluding cured/treated dermal squamous or basal cell carcinoma or cervical carcinoma in situ.
- •Women who are pregnant or lactating or, if of childbearing potential, who are unwilling to use highly effective contraception as described in this study. Male participants who are unwilling to use highly effective contraception as described in this study.
- •Known history of, or concern for, risk of hypersensitivity reaction to atumelnant or any of its excipients.
- •Participants with an increased risk of developing adrenal insufficiency as judged by the Investigator.
- •Severe erythrocytosis as judged by the Investigator.
- •Use of atumelnant prior to screening.
研究组 & 干预措施
Placebo
Matching placebo, administered orally, once daily for 32 weeks.
干预措施: Placebo (Drug)
Treatment
Atumelnant tablet, administered orally, once daily for 32 weeks.
干预措施: Atumelnant (Drug)
结局指标
主要结局
Proportion of participants with morning post-GC A4 ≤ ULN who are on physiologic GC replacement.
时间窗: Week 32
次要结局
- Percent change from baseline of morning pre-GC A4(Week 2)
- Percent change from baseline of morning pre-GC 17-OHP(Week 32)
- Proportion of participants with morning pre-GC A4 ≤ ULN who are on physiologic GC replacement(Week 32)
- Percent change from baseline in GC daily dose when morning post-GC A4 ≤ ULN(Week 32)