An Open Label Extension Study of Voxelotor (GBT440) Administered Orally to Participants With Sickle Cell Disease Who Have Participated in Voxelotor Clinical Trials
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 179
- 试验地点
- 60
- 主要终点
- Number of Participants With Sickle Cell Disease (SCD)-Related Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
Open Label Extension Study of Voxelotor Clinical Trial Participants with Sickle Cell Disease Who Participated in Voxelotor Clinical Trials
详细描述
This open label extension (OLE), multi-center study will be conducted at approximately 100 clinical sites globally and will be available to eligible participants from study GBT440-031.
The study will enroll participants from GBT440-031 (approximately 435) under any of the following conditions:
- Participant has completed 72 weeks of treatment regardless of dose selection for GBT440-031
- Dose selection has occurred for GBT440-031 and participant is on non-selected dose on GBT440-031
- GBT440-031 study interim data analysis and/or study modifications have occurred
- GBT440-031 study has completed
The objective of this open-label extension (OLE) study is to assess the long-term safety and treatment effect of voxelotor in participants who have completed treatment in study GBT440-031, using the following parameters:
- Safety based upon AEs, clinical laboratory tests, physical examinations (PE) and other clinical measures.
- Frequency of sickle cell disease (SCD)-related complications.
- Hemolytic anemia as measured by hematological laboratory parameters (e.g. hemoglobin, reticulocytes and unconjugated bilirubin).
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 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female study participants with SCD who participated and received study treatment in Study GBT440-
- •Note: Participants in GBT440-031 who discontinued study drug due to an AE, but who remained on study may be eligible for treatment in this study provided the AE does not pose a risk for treatment with voxelotor.
- •Females of child-bearing potential are required to have a negative urine pregnancy test prior to dosing on Day
- •Female participants of child-bearing potential must use highly effective methods of contraception to 30 days after the last dose of study drug. Male participants must use barrier methods of contraception to 30 days after the last dose of study drug.
- •Participant has provided written informed consent or assent (the ICF must be reviewed and signed by each participant; in the case of pediatric participants, both the consent of the participant's legal representative or legal guardian, and the participant's assent must be obtained).
排除标准
- •Female who is breast-feeding or pregnant.
- •Participant withdrew consent from Study GBT440-
- •Participant was lost to follow-up from Study GBT440-
- •Participant requiring chronic dialysis.
- •Any medical, psychological, safety, or behavioral conditions, which, in the opinion of the Investigator, may confound safety interpretation, interfere with compliance, or preclude informed consent.
研究组 & 干预措施
Voxelotor
Participants will receive voxelotor (GBT440) at the highest dose (either 900 mg or 1500 mg) deemed safe by the Data Safety Monitoring Board (DSMB).
干预措施: Voxelotor (Drug)
结局指标
主要结局
Number of Participants With Sickle Cell Disease (SCD)-Related Treatment Emergent Adverse Events (TEAEs)
时间窗: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as AEs with onset on or after the date of informed consent until 28 days after last dose of study drug. SCD-related TEAEs included preferred terms (PTs) of sickle cell anaemia with crisis, acute chest syndrome (ACS), pneumonia, priapism, and osteonecrosis. The number of participants with any SCD-related TEAEs was reported in this outcome measure.
Number of Participants With Non- SCD-Related TEAEs
时间窗: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs were defined as AEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Non-SCD-related TEAEs included all the PTs of TEAEs other than SCD- related TEAEs. The number of participants with any non-SCD-related TEAEs was reported in this outcome measure.
Number of Participants With SCD-Related Treatment Emergent Serious Adverse Events (TESAEs)
时间窗: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)
An SAE is an AE at any dose, in view of investigator resulted in any of following outcomes: death; life-threatening AE; inpatient hospitalization/prolongation of existing hospitalization; persistent/significant incapacity or disability; a congenital anomaly/birth defect and important medical events (IME) that may not result in death, be immediately life threatening; or require hospitalization may be considered serious when based upon medical judgement, they may jeopardize study participant and may require medical or surgical intervention to prevent one of outcomes listed in definition. TESAEs were defined as SAEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Number of participants with SCD-Related TESAEs was reported in this outcome measure.
Number of Participants With Non-SCD-Related TESAEs
时间窗: From date of informed consent up to 28 days after last dose of study drug (maximum up to 300.7 weeks)
An SAE is an AE at any dose, in view of investigator resulted in any of following outcomes: death; life-threatening AE; inpatient hospitalization/prolongation of existing hospitalization; persistent/significant incapacity or disability; a congenital anomaly/birth defect and IME that may not result in death, be immediately life threatening; or require hospitalization may be considered serious when based upon medical judgement, they may jeopardize study participant and may require medical or surgical intervention to prevent one of outcomes listed in definition. TESAEs were defined as SAEs with onset on or after the date of informed consent until 28 days after last dose of study drug. Number of participants with non-SCD related TESAEs was reported in this outcome measure.
Annualized Incidence Rate (Events Per Person Years) of SCD-Related Complications
时间窗: From date of informed consent up to earlier of 28 days after last dose of study drug or end of study date (maximum up to 300.7 weeks)
Annualized incidence rate was defined as total number of events (i.e. complications observed for all participants) divided by total person years. Total person-years= sum of participant summary period in years where summary period=date of informed consent until the earlier of 28 days after last dose of study drug or end of study date. SCD related complications included acute chest syndrome, cerebrovascular accident, hepatic sequestration, ocular icterus, osteonecrosis, pneumonia, priapism, pulmonary hypertension, retinopathy, sickle cell anaemia with crisis, skin ulcer and splenic sequestration. The 95% CI was based on exact Poisson confidence limits. Incidence rate of all SCD related complications is reported in this outcome measure.
Annualized Incidence Rate (VOC Events Per Person Years) of On-Treatment Vaso-occlusive Crisis (VOCs)
时间窗: From date of informed consent to last dose of study drug (maximum up to 296.7 weeks)
Annualized incidence rate was defined as total number of VOC events divided by total person years. Total person-years= sum of participant summary period in years where summary period=date of informed consent to last dose of study drug. VOC during the treatment period was defined as composite of acute painful crisis or acute chest syndrome (ACS) and included the following: moderate to severe pain lasting at least 2 hours; no explanation other than VOC; required oral or parenteral opioids, ketorolac, or other analgesics prescribed or directed by a healthcare professional. The 95% CI was based on exact Poisson confidence limits.
次要结局
- Change From Baseline in Hemoglobin Level at Week 48(Baseline, Week 48)
- Percent Change From Baseline in Reticulocytes Percentage at Week 48(Baseline, Week 48)
- Percent Change From Baseline in Absolute Reticulocytes at Week 48(Baseline, Week 48)
- Percent Change From Baseline in Indirect Bilirubin at Week 48(Baseline, Week 48)