A Pilot Study of the Effect of Etavopivat on Cerebral Hemodynamic Response in Children With Sickle Cell Disease
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Effect of etavopivat on cerebral blood flow (CBF)
研究概览
简要总结
An open-label, single arm study in patients 12 to 21 years of age with SCD to evaluate the effects of etavopivat on cerebral and muscle hemodynamics.
详细描述
This study is a pilot, open-label, single-arm study to evaluate the effect of etavopivat on cerebral hemodynamics, as measured by frequency domain near-infrared spectroscopy/diffuse correlation spectroscopy (FDNIRS/DCS) in participants 12 to 21 years of age with sickle cell disease (SCD). Cerebral blood flow (CBF), oxygen ejection fraction (OEF), and cerebral metabolic rate of oxygen (CMRO2) will be assessed FDNIRS/DCS in participants prior to, periodically throughout, and after 24 weeks of treatment with etavopivat. Approximately 12 participants will be enrolled.
The duration of study treatment will be 24 weeks. The study duration for individual participants may last up to 36 to 38 weeks and includes the Screening Period (up to 4 weeks before study treatment), the 24-week treatment period, a Safety Follow-up Visit at 4 weeks (+ 7 days) after the last dose of study drug, and an End of Study (EOS) visit approximately 8 weeks (± 7 days) after the last dose of study drug. A participant is considered to have completed the study if he or she has completed all phases of the study including the last visit or the last scheduled procedure shown in the Schedule of Events.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 21 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta0 thalassemia (HbS/β0 thal)
- •Hemoglobin (Hb): Hb ≤ 9.0 g/dL at baseline
- •Concomitant hydroxyurea (HU) therapy is allowed if the dose has been stable for at least 3 months with no anticipated need for dose adjustments during the study and no sign of hematological toxicity
排除标准
- •Any one of the following requiring a medical facility visit within 14 days prior to signing the informed consent form:
- •Vaso-occlusive crisis (VOC)
- •Acute chest syndrome (ACS)
- •Splenic sequestration
- •Dactylitis
- •Requires chronic transfusion therapy
- •Abnormal TCD in the last 12 months
- •RBC transfusion within 60 days of screening
- •Severe renal dysfunction at the Screening Visit or on chronic dialysis
- •Hepatic dysfunction
- •Clinically relevant cardiac or pulmonary disease- e.g., congenital heart defect, uncompensated heart failure, or any unstable cardiac condition, arrhythmic heart condition, pulmonary fibrosis, pulmonary hypertension
- •Major surgery involving the stomach or small intestine
- •Chemotherapy or radiation within the past 2 years
- •History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage
- •Clinically significant bacterial, fungal, parasitic, or viral infection currently receiving or that will require therapy
- •Female who is breast feeding or pregnant
研究组 & 干预措施
Etavopivat
Single-arm, open-label
干预措施: Etavopivat (Drug)
结局指标
主要结局
Effect of etavopivat on cerebral blood flow (CBF)
时间窗: 24 weeks
Change in cerebral blood flow (CBF) assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)
时间窗: 24 weeks
Change in CMRO2 assessments from baseline will be summarized with descriptive statistics by nominal study visit.
Effect of etavopivat on oxygen ejection fraction (OEF)
时间窗: 24 weeks
Change in OEF assessments from baseline will be summarized with descriptive statistics by nominal study visit.
次要结局
- Relationship between CBF and change in Hb levels(24 weeks)
- Relationship between oxygen ejection fraction (OEF) and change in Hb levels(24 weeks)
- Relationship between cerebral metabolic rate of oxygen (CMRO2) and change in Hb levels(24 weeks)
- Adverse events in participants with SCD(24 weeks)
- Muscle hemodynamic effect of etavopivat on muscle blood flow(24 weeks)
- Muscle hemodynamic effect of etavopivat on oxygen ejection fraction (OEF)(24 weeks)
- Muscle hemodynamic effect of etavopivat on cerebral metabolic rate of oxygen (CMRO2)(24 weeks)