An Adaptive, Open-Label, Dose-Finding, Phase 1/2 Study Investigating the Safety, Pharmacokinetics, and Clinical Activity of PRN1008, an Oral BTK Inhibitor, in Patients With Relapsed Immune Thrombocytopenia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 86
- 试验地点
- 51
- 主要终点
- Part A: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts by Starting Dose Level and Overall
研究概览
简要总结
This was a 2 part (Part A and B) adaptive, open-label, dose-finding study of PRN1008 in patients with ITP who are refractory or relapsed with no available and approved therapeutic options, with a platelet count <30,000/μL on two counts no sooner than 7 days apart in the 15 days before treatment begins. The dose-finding portion of the study was completed. Part B treatment dose was 400 mg twice daily.
详细描述
This was a 2 part (Part A and B) adaptive, open-label, dose-finding study of PRN1008 in approximately 60 patients in Part A and approximately 25 patients in Part B.
Part A enrolled patients with ITP who were refractory or relapsed with no available and approved therapeutic options. Eligible patients had a platelet count <30,000/μL on two counts no sooner than 7 days apart in the 15 days before treatment begins. The active treatment period was 24 weeks and the post-treatment follow-up period is 4 weeks. In the dose-finding part of the study, each patient enrolled in the study was allowed to up-titrate their dose after 28 days of PRN1008 therapy, if they did not experience a platelet response or a dose-limiting toxicity (DLT) at the last dose level. Patients who responded to PRN1008 per protocol may enter a long term-extension.
Part B of the study included approximately 25 patients with ITP who had relapsed or had an insufficient response to prior therapies. Eligible patients had a platelet count <30,000/µL on two occasions no less than 7 days apart, within 15 days before treatment began and a platelet count of ≤35,000/µL on Study Day 1 (SD1). The study consisted of a 28-day screening period, 24-week active treatment period, and a long-term extension. After the last dose of PRN1008 there was a 4-week safety follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients, aged 18 to 80 years old
- •Immune-related ITP (both primary and secondary)
排除标准
- •Pregnant or lactating women
- •Current drug or alcohol abuse
- •History of solid organ transplant
- •Positive screening for HIV, hepatitis B, or hepatitis C
研究组 & 干预措施
Rilzabrutinib (PRN1008) Daily
Part A approximately 60 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension.
Part B approximately 25 patients: Up to 24 weeks open-label treatment with PRN1008 400mg BID; safety and dose evaluation. Patients who respond to PRN1008 per protocol may enter a long-term extension
干预措施: Rilzabrutinib (Drug)
结局指标
主要结局
Part A: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts by Starting Dose Level and Overall
时间窗: Up to 24 Weeks
The percentage of participants who achieved 2 or more consecutive platelet counts, separated by at least 5 days, of \>=50,000/ microliter (μL) and an increase of platelet count of \>=20,000/μL from baseline, by starting dose level and overall, without use of rescue medication in the 4 weeks prior to the latest elevated platelet count. 95% confidence interval (CI) was based on the Clopper-Pearson method. The average of the 2 screening results and the Cycle 1 Day 1 result were used as the baseline value.
Part B: Percentage of Participants Who Achieved Platelet Counts >=50,000/μL
时间窗: Up to 24 Weeks
The percentage of participants who achieved platelet counts \>=50,000/μL on at least 8 out of the last 12 weeks of the 24-week treatment period without the use of rescue medication after 10 weeks of active treatment. 95% CI was based on the Clopper-Pearson exact method.
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Treatment-Emergent Adverse Events
时间窗: From first dose of rilzabrutinib (Day 1) up to last dose + 1 (up to 294 days)
Adverse event (AE): any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious on or after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to the rilzabrutinib.
Part B: Number of Participants With Treatment-Emergent Adverse Events and Treatment Related Treatment-Emergent Adverse Events
时间窗: From first dose of rilzabrutinib (Day 1) up to last dose + 1 (approximately 170 days)
AE any untoward medical occurrence in participant or clinical study participant, temporally associated with the use of rilzabrutinib, whether or not considered related to rilzabrutinib. TEAEs: AEs that developed or worsened or became serious during the treatment-emergent period, defined as any time after the first dose administration of rilzabrutinib (Day 1). Any TEAEs are considered treatment-related TEAEs as per Investigator's evaluation of participant's circumstances surrounding the event, and an evaluation of any potential alternative causes to determine whether an TEAE can be considered as related to rilzabrutinib.
次要结局
- Part A: Time to First Platelet Count >=50,000/μL Across All Dose Levels(Up to 24 Weeks)
- Part B: Percentage of Participants Who Received Rescue Medication(Up to 24 Weeks)
- Part A: Percentage of Participants With Grade 2 or Higher Bleeding Event by Dose Level and Overall(Up to 24 Weeks)
- Part A: Percentage of Weeks With Platelet Counts >=50,000/μL by Starting Dose Level and Overall(Up to 24 Weeks)
- Part B: Number of Weeks With Platelet Counts >= 50,000/μL or >= 30,000/μL and Doubling the Baseline(Up to 24 Weeks)
- Part B: Percentage of Participants Who Achieved 2 or More Consecutive Platelet Counts(Up to 24 Weeks)
- Part B: Number of Weeks With Platelet Counts >=30,000/μL and Doubling the Baseline(Up to 24 Weeks)
- Part A: Percentage of Participants With 4 Out of the Final 8 Platelet Counts >=50,000/μL by Starting Dose Level and Overall(Up to 24 Weeks)
- Part A: Change From Baseline to the Average of Post Day 1 Platelet Counts by Dose Level and Overall(Baseline and up to 24 Weeks)
- Part A: Number of Weeks With Platelet Counts >=50,000/μL by Starting Dose Level and Overall(Up to 24 Weeks)
- Part A: Number of Weeks With Platelet Counts >=30,000/μL by Starting Dose Level and Overall(Up to 24 Weeks)
- Part B: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS)(Baseline and up to 24 weeks)
- Part A: Percentage of Participants Who Received Rescue Medication by Dose Levels and Overall(Up to 24 Weeks)
- Part A: Number of Participants With Idiopathic Thrombocytopenic Purpura/Immune Thrombocytopenia (ITP) Bleeding Assessment Tool (ITP-BAT) Scale by Dose Level(Up to 24 Weeks)
- Part A: Maximum Observed Plasma Concentration (Cmax) of Rilzabrutinib(Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days))
- Part A: Time of Observed Maximum Plasma Concentration (Tmax) of Rilzabrutinib(Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days))
- Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of Rilzabrutinib(Day 1 of Cycles 1, 2, 3, and 5 (each cycle 28 days))
- Part A: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Rilzabrutinib(Day 1 of Cycles 1, 2, and 3 (each cycle 28 days))
- Part A: Elimination Half-Life (t1/2) of Rilzabrutinib(Day 1 of Cycles 1, 2, and 3 (each cycle 28 days))
- Part A: Apparent Volume of Distribution of the Drug After Oral Administration (Vz/F) of Rilzabrutinib(Day 1 of Cycles 1, 2, and 3 (each cycle 28 days))
- Part A: Apparent Total Clearance of the Drug From Plasma After Oral Administration (CL/F) of Rilzabrutinib(Day 1 of Cycles 1, 2, and 3 (each cycle 28 days))
- Part B: Plasma Concentration of Rilzabrutinib(Pre-dose and 2 hours post-dose on Days 1, 29, and 57)