A Phase 2, Multiple-Dose, Dose-Escalation Study to Evaluate the Safety and Efficacy of SPR001 in Adults With Classic Congenital Adrenal Hyperplasia (CAH)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Safety of SPR001 in Patients With CAH
研究概览
简要总结
This is a multicenter Phase 2, multiple dose, dose escalation study to evaluate the safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of SPR001 in adult patients with classic congenital adrenal hyperplasia (CAH).
详细描述
This is a 6-week, multiple-dose, dose escalation study of SPR001 for the treatment of adults with classic CAH. After screening, eligible patients will be enrolled into a 6-week treatment period followed by a 4-week washout/safety follow-up period.
It is initially planned that up to approximately 18 patients in 2 dose cohorts will be enrolled. Additional patients or dose groups may be considered based upon specific safety, PK/PD, and/or efficacy findings, or if an active dose has not yet been reached.
SPR001 will be administered as an oral daily dose. Patients will undergo titration of SPR001 through three escalating dosage strengths at 2-week intervals. Patients will have overnight PK/PD assessments performed at baseline, which include an pre-dose overnight assessment and a post-dose overnight assessment for PK/PD following administration of the first dose. At the end of each 2-week dosing period, patients will return for single overnight visits for steady-state PK/PD assessments.
A follow-up outpatient visit will occur 30 days after their last dose.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female patients age 18 or older.
- •Documented diagnosis of classic CAH due to 21-hydroxylase deficiency
- •Elevated 17-OHP at screening
- •On a stable glucocorticoid replacement regimen for a minimum of 30 days
排除标准
- •Clinically significant unstable medical condition, illness, or chronic disease
- •Clinically significant psychiatric disorder.
- •Clinically significant abnormal laboratory finding or assessment
- •History of bilateral adrenalectomy or hypopituitarism
- •Pregnant or nursing females
- •Use of any other investigational drug within 30 days
- •Unable to understand and comply with the study procedures, understand the risks, and/or unwilling to provide written informed consent.
研究组 & 干预措施
Cohort A
The first cohort of 9 patients will be administered SPR001 at dose strength of Dose A daily for 2 weeks, and escalating through Dose B per day for 2 weeks and Dose C per day for 2 weeks.
干预措施: SPR001 (Drug)
Cohort B
Cohort B will begin enrollment after Cohort A has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort B will be determined by an interim review of safety and PK/PD data from from Cohort A.
干预措施: SPR001 (Drug)
Cohort C
Cohort C will begin enrollment after Cohort B has been fully enrolled. Starting dose selection and the stepwise dosing paradigm for Cohort C will be determined by an interim review of safety and PK/PD data from from Cohort A and B.
干预措施: SPR001 (Drug)
结局指标
主要结局
Safety of SPR001 in Patients With CAH
时间窗: 6 weeks
Incidence of treatment-emergent adverse events, changes from Baseline to End-of-study in clinical laboratory parameters, physical examination findings, vital signs, ECG parameters
Change in 17-hydroxyprogesterone
时间窗: Cohort A: Baseline/2a (Day -1-0), First dose/2b (Day 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41-42). Cohort B and Cohort C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 14-15), Visit 5 (Last dose +30d)
Change in 17-hydroxyprogesterone from Baseline to End-of-study. Results are expressed as mean percent change from baseline. Reductions in 17-OHP are indicators of better disease control.
次要结局
- Changes in Pharmacodynamic (PD) Markers(Cohort A: Visit 2a (Day -1 to 0), Visit 2b (Days 0-1), Visit 3 (Day 13-14), Visit 4 (Day 27-28), Visit 5 (Day 41 to 42). Cohorts B+C: Visit 2 (Day 0-1), Visit 3 (Day 8), Visit 4 (Day 27-28), Visit 5 (+30 days after last dose))
- Pharmacokinetic Parameter - Maximum Plasma Concentration (Cmax)(Serial PK sampling was performed at the end of the 2 weeks for all cohorts and dose levels)
- Pharmacokinetic Parameter - Area Under the Concentration-time Curve (AUC)(For Cohort A, serial blood collections were made for PK measurements on Day 1 for 200 mg SD and at Week 2 for all QD dose levels. In Cohorts B and C, serial blood samples were drawn for PK measurements at the end of the 2-week treatment period.)