A Phase 1 Open-Label, Dose-Escalation Study to Evaluate Safety, Pharmacokinetic, and Biological Activity of INCB059872 in Subjects With Sickle Cell Disease
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 12
- 试验地点
- 7
- 主要终点
- Change in fetal hemoglobin (HbF) from baseline
研究概览
简要总结
The purpose of this study was to evaluate the safety and tolerability, and the pharmacokinetic and biologic activity of INCB059872 in participants with sickle cell disease.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Diagnosis of SCD (sickle cell SS) confirmed through hemoglobin electrophoresis.
- •Must be red blood cell (RBC) transfusion-independent (not currently on regularly scheduled transfusions) for ≥ 3 months from the time of first dose of study drug.
- •No RBC transfusion within 30 days of first dose of study drug.
- •Hydroxyurea (HU) refractory
- •Must not have received HU therapy during the 3 months before receiving study drug.
- •Creatinine clearance ≥ 60 mL/min based on the institutional formula.
- •Willingness to avoid pregnancy or fathering children.
排除标准
- •Any unresolved toxicity ≥ Grade 2 from previous therapy except for stable chronic toxicities not expected to resolve.
- •Pregnant or nursing women or participants expecting to conceive or father children within the projected duration of the study, starting with screening visit through completion of safety follow-up.
- •Received an investigational study drug within 28 days or 5 half-lives (whichever is longer) before receiving the first dose of study drug (requirement may be waived with medical monitor approval).
- •Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment.
- •Prior receipt of LSD1 inhibitor therapy for any indication.
研究组 & 干预措施
INCB059872 0.5 mg
INCB059872 0.5 mg tablet administered orally every other day (QOD) for 28 days on an empty stomach. If dose was well tolerated, once daily (QD) administration was evaluated independently and in parallel with QOD administration.
干预措施: INCB059872 (Drug)
INCB059872 1 mg
INCB059872 1 mg tablet administered orally QOD for 28 days on an empty stomach. If dose was well tolerated, QD administration was evaluated independently and in parallel with QOD administration.
干预措施: INCB059872 (Drug)
INCB059872 2 mg
INCB059872 2 mg tablet administered orally QOD for 28 days on an empty stomach. If dose was well tolerated, QD administration was evaluated independently and in parallel with QOD administration.
干预措施: INCB059872 (Drug)
结局指标
主要结局
Change in fetal hemoglobin (HbF) from baseline
时间窗: Baseline through 2 weeks after end of treatment, up to approximately 2.5 months per participant.
Pharmacodynamic activity assessed by measuring changes of HbF from baseline and their correlation to INCB059872 treatment. The HbF (F cells) in human whole blood will be characterized using flow cytometry.
Safety and tolerability of INCB059872 assessed by monitoring frequency, duration, and severity of adverse events
时间窗: Screening through 35 days after end of treatment, up to approximately 3 months per participant.
An adverse event is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a participant provides informed consent.
次要结局
- Cmax of INCB059872(Baseline to Day 28.)
- AUC0-t of INCB059872(Baseline to Day 28.)