A PHASE 2/3 RANDOMIZED, MULTICENTER STUDY OF OSIVELOTOR ADMINISTERED ORALLY TO ADULT AND ADOLESCENT PARTICIPANTS WITH SICKLE CELL DISEASE
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Pfizer
- 入组人数
- 389
- 试验地点
- 101
- 主要终点
- Part A
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of osivelotor.
详细描述
This is a three-part, multicenter, Phase 2/3 study of orally administered osivelotor in participants with sickle cell disease (SCD).
Part A will evaluate the safety, tolerability, and efficacy of osivelotor in adult participants with SCD to determine an optimal dose. (Complete) Part B will evaluate the efficacy of osivelotor versus placebo in adult and adolescent participants with SCD for 48 weeks.
Open Label Extension (OLE) will evaluate the long-term safety and hematologic responses of open-label osivelotor in adult and adolescent participants having completed Part B.
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
Part B only
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Part A and Part B:
- •Male or female with SCD, HbSS and HbSB-zero
- •Participants with Hemoglobin ≥ 5.5 and ≤ 10.5 g/dL during Screening and considered stable by the Investigator.
- •For participants taking hydroxyurea and/or L-glutamine, the dose must be stable for at least 90 days prior to signing the ICF or assent and with no anticipated need for dose adjustments during the study in the opinion of the Investigator.
- •Participants with SCD ages 12 years and older, inclusive at screening.
- •Participants with more than or equal to 2 and ≤ 10 VOCs within 12 months of Screening.
- •- Participants who have completed the Part B successfully will be eligible.
排除标准
- •Part A and Part B:
- •Participants who had more than 10 VOC within 12 months of screening
- •Female participant who is breastfeeding or pregnant
- •Participants who receive RBC transfusion therapy regularly or received an RBC transfusion ---for any reason within 90 days of Day 1
- •Participants hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF or anytime during the screening period.
- •Participants in Sub-Saharan Africa or who have relocated from Sub-Saharan Africa within 6 months.
- •Have any unresolved clinically significant adverse event, laboratory abnormality, or safety finding from Part B that, in the opinion of the Investigator, increases the risk of study drug administration.
- •Met permanent treatment discontinuation criteria during Part B.
- •Have withdrawn consent or are unable to comply with study procedure
研究组 & 干预措施
Part A
Initially, participants will be randomized 1:1 to 100 mg and 150 mg daily. Upon review of the 150 mg safety data from at least 6 participants, there will be 1:1:1 randomization: 100 mg, 150 mg, and up to 200 mg.
Participants will then receive maintenance once daily doses through Week 12.
干预措施: Osivelotor (Drug)
Part B
Study drug arm: Adult participants will receive osivelotor at 300 mg QD loading dose for 7 days followed by 150 mg QD through Week 48.
Adolescent participant dose will be defined in a future protocol amendment.
Placebo arm: Participants will receive placebo tablets for 48 weeks.
干预措施: Osivelotor (Drug)
OLE
Adult Participants will receive 150 mg open-label osivelotor up to 2 years after the last participant's visit in Part B or when the drug is commercially available in that region.
The appropriate doses for adolescents will be defined in a future protocol amendment.
干预措施: Osivelotor (Drug)
结局指标
主要结局
Part A
时间窗: Through week 12
Number of adult participants with change from baseline in hemoglobin (Hb) through week 12 as measured by change in osivelotor concentrations from baseline or percentage change from baseline of clinical measures of anemia Hb and hemolysis (including indirect bilirubin, reticulocytes and lactate dehydrogenase).
Part B
时间窗: Through week 48
Co-primary endpoints: Hb response (increase from baseline of \>1 g/dL) at Week 48 (based on average of Hb levels at Week 40 and Week 48) and the Annualized rate of VOC through end of Week 48. A VOC is defined as an acute episode of pain that: * Has no medically determined cause other than a vaso-occlusive event, and * Results in a visit to a medical facility (hospitalization, emergency department, urgent care center, outpatient clinic, or infusion center), and * Requires parenteral narcotic agents, parenteral nonsteroidal anti-inflammatory drugs (NSAIDs), or an increase in treatment with oral narcotics. Complicated VOCs of acute chest syndrome (ACS), hepatic sequestration, splenic sequestration, priapism, and dactylitis that meet the requirements listed above will be included in this co-primary endpoint.
OLE
时间窗: Approximately 24 months after last patient enrolled
Incidence of Treatment Emergent Adverse Events: * Incidence of SAEs * Incidence of AEs leading to discontinuation * Change from baseline in laboratory parameters.
次要结局
未报告次要终点