A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Voxelotor (GBT440) in Pediatric Participants With Sickle Cell Disease (HOPE Kids 2)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 236
- 试验地点
- 35
- 主要终点
- Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24
研究概览
简要总结
This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to < 15 years old, with Sickle Cell Disease. The primary objective is to evaluate the effect of voxelotor on the TCD (Transcranial Doppler Ultrasound) measurements in SCD participants in this age range.
详细描述
This study is a Phase 3, randomized, double-blind, placebo-controlled study of voxelotor in pediatric participants, aged ≥ 2 to < 15 years old, with Sickle Cell Disease. The study will be conducted at approximately 50 international clinical sites, and will enroll approximately 224 participants. Participants will be randomized in a 1:1 ratio to receive voxelotor or placebo. All participants younger than 12 years of age and randomized to voxelotor will receive a dose based on their body weight, to provide exposure corresponding to the adult dose of 1500 mg/day.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-Blind, Placebo-Controlled
入排标准
- 年龄范围
- 2 Years 至 14 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants with Sickle Cell Anemia (SCA) HbSS, HbSβ0 thalassemia genotype
- •TCD time averaged maximum of the mean velocity (TAMMV) arterial cerebral blood flow ≥ 170 to < 200cm/sec during the Screening Period
- •Hb ≥ 5.5 and ≤ 10.5 g/dL during screening
- •For participants taking HU, the dose of HU (mg/kg) must be stable for at least 90 days prior to signing the informed consent form (ICF) and/or assent form, and with no anticipated need for dose adjustments (other than weight based) or for initiation of HU for non-chronic use during the study, in the opinion of the Investigator
- •Written informed parental/guardian consent and participant assent (where applicable) has been obtained per IRB/EC policy and requirements, consistent with ICH guidelines.
排除标准
- •Body weight < 10kg at the screening visit
- •Hospitalization for VOC or acute chest syndrome (ACS) within the 14 days prior to execution of informed consent/assent
- •More than 10 VOCs within the past 12 months that required hospitalization, emergency room, or clinic visit
- •Stroke resulting in focal neurological deficit; previous silent infarcts are permitted.
- •Known history or findings suggestive of significant cerebral vasculopathy
- •History of seizure disorder
- •Has been treated with erythropoietin or other hematopoietic growth factors within 28 days of signing informed consent/assent or if, in the opinion of the Investigator, there is an anticipated need for such agents during the study
- •RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion) or has received an RBC transfusion or exchange transfusion for any reason within 90 days of signing the informed consent/assent
研究组 & 干预措施
Voxelotor
Voxelotor 1500mg or equivalent daily as a tablet, dispersible tablet, or as powder for oral suspension.
干预措施: Voxelotor (Drug)
Placebo
Matching placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Time-Averaged Maximum of Mean Velocity (TAMMV) Arterial Cerebral Blood Flow at Week 24
时间窗: Baseline (value at screening), Week 24
TAMMV is an ultrasound measurement used in transcranial Doppler (TCD) to assess blood flow in cerebral arteries. TCD flow velocities were categorized as follows: (i) Normal: \< 170 centimeter per second (cm/sec); (ii) Conditional: 170 to \< 200 cm/sec - the eligible participant population for this study; (iii) Abnormal: \>= 200 cm/sec.
次要结局
- Change From Baseline in TAMMV Arterial Cerebral Blood Flow at Week 48(Baseline (value at Screening), Weeks 48)
- Time to Conversion to Abnormal TCD Flow(Up to 96 weeks)
- Time to Reversion to Normal TCD Flow(Up to 96 weeks)
- Percentage of Participants With TAMMV Reduced by >=15 cm/Sec From Baseline at Weeks 24, 48 and 96(At Weeks 24, 48 and 96)
- Change From Baseline in Hemoglobin (Hb) at Weeks 24, 48 and 96(Baseline (value at Screening), Weeks 24, 48 and 96)
- Percent Change From Baseline in Unconjugated Bilirubin at Weeks 24, 48 and 96(Baseline (value at Screening), Weeks 24, 48 and 96)
- Percent Change From Baseline in Reticulocyte at Weeks 24, 48 and 96(Baseline (value at Screening), Weeks 24, 48 and 96)
- Percent Change From Baseline in Absolute Reticulocyte at Weeks 24, 48 and 96(Baseline (value at Screening), Weeks 24, 48 and 96)
- Percent Change From Baseline in Lactate Dehydrogenase (LDH) at Weeks 24, 48 and 96(Baseline (value at Screening), Weeks 24, 48 and 96)
- Annualized Incidence Rate of Vaso-Occlusive Crises (VOCs)(From randomization to the last dose date, post-randomization HU initiation with no HU at baseline, end of study or study termination, whichever occurred earlier (maximum up to 110 weeks))