A Phase 3, Double-Blind, Randomized, Efficacy and Safety Comparison of Prasugrel and Placebo in Pediatric Patients With Sickle Cell Disease.
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 341
- 试验地点
- 21
- 主要终点
- Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC)
研究概览
简要总结
The main purpose of the study is to evaluate the efficacy and safety of the study drug known as prasugrel for the reduction of Vaso-Occlusive Crisis events in pediatric participants with sickle cell disease. The study will also investigate reduction in daily pain in children who have sickle cell disease.
详细描述
The submission database was validated for data reported through the data cutoff date for the submission database lock (SDBL). The SDBL data cutoff was 17 July 2015 for all participants except for 2 in the youngest age group, for whom the SDBL data cutoff occurred on 08 August 2015. The data cutoff date for SDBL corresponds to the primary completion date for the study. The SDBL occurred on 31 August 2015.
The study was stopped following SDBL and review of the topline information indicated that the primary and secondary efficacy endpoints were not met. Subsequently, the Sponsor requested that participants discontinue study drug immediately and that discontinuation visits for all active study participants be conducted as soon as feasible.
After the data cutoff date for SDBL, the Sponsor continued to collect safety data through the final participants contact; some additional efficacy data were collected through the final visit. The last patient visit (LPV) occurred on 17 December 2015, which corresponds to the study completion date and led to the planned supplemental database lock (PSDBL) on 22 January 2016. This supplemental data base was originally designed to capture additional blinded and randomized information to enhance safety data for labeling should the study have been positive.
The safety information contained in this record reflects the entire safety information and reflects the information from the supplemental data base lock in January of 2016. The efficacy information contained in this record reflects the information collected through primary completion date in the submission database. Primary analyses of the major efficacy objectives were repeated using the entire double-blind period data from the PSDBL and did not change the original conclusions and were consistent with the results from the original efficacy analyses included in the SDBL.
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 2 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have SCD [homozygous sickle cell (HbSS) or hemoglobin (HbS) Beta^0 thalassemia]
- •Are participants with SCD who have had ≥2 episodes of vaso-occlusive crisis (VOC) in the past year
- •Have a body weight ≥19 kilograms (kg) and are ≥2 and <18 years of age, inclusive at the time of screening
- •If participants are ≥2 and ≤16 years of age, must have had a transcranial Doppler within the last year
排除标准
- •History of: transient ischemic attack (TIA)/ ischemic or hemorrhagic stroke, severe head trauma, intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm
- •History of abnormal or conditional [velocity in middle or anterior cerebral, or internal carotid artery ≥170 centimeter per second (cm/sec)] transcranial Doppler within the last year
- •History of, or are undergoing treatment with, chronic red blood cell (RBC) transfusion therapy
- •Are at an increased risk for bleeding complications
- •Are receiving chronic treatment with nonsteroidal anti-inflammatory drug (NSAID)s and cannot be switched to another analgesic
研究组 & 干预措施
Prasugrel
Participants will be titrated from initial daily dose of 0.08 milligram per kilogram (mg/kg) of orally administered prasugrel monotherapy at randomization to a dose that will achieve a P2Y12 reaction units (PRU) level of 231 to 136, as measured by VerifyNow instrument. This corresponds to a range of platelet inhibition of approximately 30% to 60%. The maximum possible dose allowed is 0.12 mg/kg daily, not to exceed 10 mg daily.
干预措施: Prasugrel (Drug)
Placebo
Participants in this treatment group will receive daily orally administered placebo and will follow visit schedule identical to that in the active treatment group.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Vaso-Occlusive Crisis (VOC) Events Per Participant Per Year (Rate of VOC)
时间窗: Randomization through 24 Months
The VOC is a composite endpoint of painful crisis or acute chest syndrome. Events that occurred within 7 days from the prior event onset date were not counted as a new episode. Data collected through the primary completion date reported below.
次要结局
- Monthly Mean in Faces Pain Scale-Revised Score(Randomization through 9 Months)
- Number of Hospitalizations for VOC Per Participant Per Year (Rate of Hospitalizations)(Randomization through 24 Months)
- Number of Red Blood Cell (RBC) Transfusions Due to Sickle Cell Disease (SCD) Per Participant Per Year (Rate of RBC Transfusions)(Randomization through 24 Months)
- Monthly Rate of Days With Pain(Randomization through 9 Months)
- Number of Painful Crisis Events Per Participant Per Year (Rate of Painful Crisis)(Randomization through 24 Months)
- Number of Acute Chest Syndrome Per Participant Per Year (Rate of Acute Chest Syndrome)(Randomization through 24 Months)
- Number of Days Hospitalized for VOC(Randomization through 24 Months)
- Monthly Rate of Days of Analgesic Use(Randomization through 9 Months)
- Quarterly Rate of School Absence Due to Sickle Cell Pain(Randomization through 9 Months)
- Time to First Transient Ischemic Attack (TIA)/Ischemic Stroke(Randomization through 24 Months)
- Percentage of Participants With Hemorrhagic Events Requiring Medical Intervention(First Dose through 24 Months)
- Time From Randomization to First and Second VOC(Randomization to First VOC and Second VOC respectively (up to 24 Months))