A Multi-site, Open-label, Sequential-group, Multiple-dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamic Effects of Lu AG13909 in Participants With Congenital Adrenal Hyperplasia
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 42
- 试验地点
- 22
- 主要终点
- Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
This trial will evaluate the effects of different doses of Lu AG13909 in adult participants with congenital adrenal hyperplasia, also called CAH. CAH is a rare genetic disorder that affects a person's ability to produce certain hormones. The main goals of this trial are to learn about the safety and tolerability of Lu AG13909, how Lu AG13909 behaves in the body, and how the body responds to Lu AG13909.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parts A and B:
- •Confirmed diagnosis of 21-hydroxylase deficiency CAH (based on a pathogenic CYP21A2 variant and/or elevated 17-OHP).
- •Morning (pre-glucocorticoid [GC] replacement dose) blood concentrations of 17-OHP >4-times upper limit of normal (ULN).
- •Body mass index (BMI) ≥18.5 kilograms (kg)/square meter (m^2) (minimum 50 kg) and ≤40 kg/m^
- •Stable GC replacement therapy for ≥1 month prior to the Screening Visit.
- •For the salt-wasting form of CAH, the participant must have been on a stable dose of mineralocorticoid replacement for ≥3 months prior to the Screening Visit.
- •Apart from CAH, the participant is generally healthy in the opinion of the investigator and based on medical history, physical examination, vital signs, ECGs, and the results of the safety laboratory tests.
- •Confirmed diagnosis of 21-hydroxylase deficiency CAH (based on a pathogenic CYP21A2 variant and/or elevated 17-OHP).
- •For Cohort C1 only: Morning (pre-GC replacement dose) blood concentrations of androgens (A4) > ULN for age and sex.
- •For Cohort C2 only: Morning (pre-GC replacement dose) blood concentrations of androgens (A4) ≤ ULN for age and sex and the participant is treated with high doses of GC.
- •Stable GC replacement therapy for ≥1 month prior to the Screening Visit.
- •For the salt-wasting form of CAH, the participant must have been on a stable dose of mineralocorticoid replacement for ≥1 month prior to the Screening Visit.
排除标准
- •The participant is pregnant or breastfeeding.
- •The participant has a clinically significant abnormal laboratory value, electrocardiogram (ECG) parameter, or vital signs value, or other safety findings at the Screening Visit that indicate a potential risk for the participant if enrolled, in the opinion of the investigator.
- •The participant has a history of known hypersensitivity or intolerance to Lu AG13909 or its excipients.
- •Part C Only:
- •The participant has received at least one dose of Lu AG13909 in Part A or Part B.
- •Other inclusion and exclusion criteria may apply.
研究组 & 干预措施
Lu AG13909
Participants in Part A will receive multiple intravenous (IV) doses of Lu AG13909 per a prespecified dosing schedule. After data from Part A has shown that a pharmacologically relevant dose level is safe and tolerable, participants in Part B will then receive multiple IV doses of Lu AG13909 per a prespecified dosing schedule. After data from Part B has shown that a pharmacologically relevant dose level is safe and tolerable, participants in Part C will then receive multiple IV doses of Lu AG13909 per a prespecified dosing schedule. Participants from Part C may be eligible to continue in the optional Treatment Extension.
干预措施: Lu AG13909 (Drug)
结局指标
主要结局
Parts A and B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to Day 161
Parts A and B: Number of Participants With Anti-Drug Antibodies (ADAs)
时间窗: Day 1 up to Day 161
Parts A and B: Cmax: Maximum Observed Serum Concentration of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: Tmax: Nominal Time Corresponding to the Occurrence of Cmax
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: Ctrough: Minimum Observed Serum Concentration of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: t½: Apparent Elimination Half-life of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: AUC0-infinity: Area under the plasma concentration curve of x from zero to infinity of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: CL: Apparent Total Serum Clearance of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: Vz: Volume of Distribution During the Terminal Elimination Phase After IV Administration of Lu AG13909
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Parts A and B: Change From Baseline After Each Dose of Lu AG13909 in Blood Concentrations of 17-hydroxyprogesterone (17-OHP) and Androstenedione (A4)
时间窗: Baseline up to Day 85
Parts A and B: AUC0-tau: Area under the curve over a dosing interval
时间窗: 0 (predose) up to 24 hours postdose on Day 1 to Day 161
Part C: Morning Concentration of A4 in Blood <Upper Limit of Normal (ULN)
时间窗: Day 169
次要结局
- Part C: Lu AG13909 Serum Concentrations Following Multiple IV Doses(Baseline up to Day 352)
- Part C: Change From Baseline of Lu AG13909 in Blood Concentrations of 17-OHP and A4(Baseline up to Day 169)
- Part C: Number of Participants With TEAEs(Baseline up to Day 352)
- Part C: Number of Participants With ADAs(Baseline up to Day 352)