NCT04603495进行中（未招募）3 期
A Phase 3, Randomized, Double-blind, Active-Control Study of Pelabresib (CPI-0610) and Ruxolitinib vs. Placebo and Ruxolitinib in JAKi Treatment Naive MF Patients
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 430
- 试验地点
- 273
- 主要终点
- Number of Participants With Splenic Response by Central Radiology Reads at Week 24
研究概览
简要总结
A Phase 3, randomized, blinded study comparing pelabresib (CPI-0610) and ruxolitinib with placebo and ruxolitinib in myelofibrosis (MF) patients that have not been previously treated with Janus kinase inhibitors (JAKi). Pelabresib is a small molecule inhibitor of bromodomain and extra-terminal (BET) proteins.
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
This study has a double-blind design in which patients and investigators are blinded to study drug; study drugs will be packaged identically. All patients will be randomly assigned to either treatment group in a 1:1 ratio. The blind should only be broken in the case of emergency.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged ≥ 18 years
- •Confirmed diagnosis of myelofibrosis (primary, post-polycythemia vera, or post essential thrombocythemia)
- •Adequate hematologic, renal, and hepatic function
- •Have at least 2 symptoms with an average score ≥ 3 or an average total score of ≥ 10 over the 7-day period prior to randomization using the MFSAF v4.0
- •Prognostic risk-factor score of Intermediate-1 or higher per Dynamic International Prognostic Scoring System (DIPSS) scoring system
- •Spleen volume of ≥ 450 cm^3
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
排除标准
- •Splenectomy or splenic irradiation in the previous 6 months
- •Chronic or active conditions and/or concomitant medication use that would prohibit treatment
- •Had prior treatment with any JAKi or BET inhibitor for treatment of a myeloproliferative neoplasm
研究组 & 干预措施
Pelabresib + ruxolitinib
Experimental
Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
干预措施: Pelabresib (Drug)
Pelabresib + ruxolitinib
Experimental
Pelabresib monohydrate tablets + ruxolitinib phosphate tablets
干预措施: Ruxolitinib (Drug)
Placebo + ruxolitinib
Active Comparator
Matching placebo tablets + ruxolitinib phosphate tablets
干预措施: Ruxolitinib (Drug)
Placebo + ruxolitinib
Active Comparator
Matching placebo tablets + ruxolitinib phosphate tablets
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Splenic Response by Central Radiology Reads at Week 24
时间窗: Week 24
Splenic response was characterized by a reduction of at least 35% in spleen volume from baseline (SVR35), as determined by magnetic resonance imaging (MRI) or computerized tomography (CT), and evaluated through a blinded central radiology review at Week 24.
次要结局
- Key Secondary: Number of Participants With TSS50 Response at Week 24(Week 24)
- Key Secondary: Absolute Change From Baseline in Total Symptom Score (TSS) at Week 24(Baseline, Week 24)
- Percent Change From Baseline in Total Symptom Score (TSS) at Week 24(Baseline, Week 24)
- Number of Participants With Improvement From Baseline in Bone Marrow Fibrosis of at Least 1 Grade at Week 24(Baseline, Week 24)
- Number of Participants With Splenic Response by Central Radiology Reads at Week 48(Week 48)
- Number of Participants With TSS50 Response at Week 48(Week 48)
- Absolute Change From Baseline in Total Symptom Score (TSS) at Week 48(Baseline, Week 48)
- Rate of Red Blood Cell (RBC) Transfusion Over First 24 Weeks of Treatment(Week 24)
- Number of Participants Who Transitioned From Red Blood Cell (RBC) Transfusion Dependence to Transfusion Independence(From 12-week baseline period prior to dosing to any 12-week period post baseline, up to 24 weeks)
- Category Change From Baseline of Patient Global Impression of Change (PGIC) at Week 24(Baseline, Week 24)
- Progression-Free Survival (PFS)(Through study completion, an average of 6 years)
- Overall Survival (OS)(Through study completion, an average of 6 years)
- Proportion of Patients With Transformation to Blast Phase (AML)(Through study completion, an average of 6 years)
- Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(Through study completion, an average of 6 years)
- Pharmacokinetic (PK) Parameters for Pelabresib: Area Under the Plasma Concentration-time Curve From Time Zero to Time t (AUC0-t)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Pharmacokinetic (PK) Parameters for Pelabresib: Time to Reach Maximum (Peak) Plasma Concentration Following Drug Administration (Tmax)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Pharmacokinetic (PK) Parameters for Pelabresib: Maximum (Peak) Plasma Drug Concentration (Cmax)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Pharmacokinetic (PK) Parameters for Pelabresib: Effective Half-Life (T1/2)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Pharmacokinetic (PK) Parameters for Pelabresib: Apparent Volume of Distribution After Non-intravenous Administration (Vd/F)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Pharmacokinetic (PK) Parameters for Pelabresib: Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F)(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Ruxolitinib Plasma Concentrations in the Presence or Absence of Pelabresib(Cycle 1 Day 1, Cycle 1 Day 14 and Cycle 9 Day 1: Predose, 30 minutes to 1 hour post-dose, 3 to 4.5 hours post-dose. Cycle 3 and Cycle 7 Day 1: Predose, 5 minutes post ECG assessment. 1 Cycle = 21 days)
- Duration of the Splenic Response(Through study completion, an average of 6 years)
- Number of Participants With Modified Total Symptom Score (mTSS) Response at Week 24(Week 24)
- Duration of the TSS50 Response(Through study completion, an average of 6 years)
研究者
研究点 (273)
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