A Phase 3, Multicenter, Randomized, Double-Blind, Placebo Controlled, Parallel-Group Study With an Open-Label Extension to Evaluate the Efficacy and Safety of Oral Rilzabrutinib (PRN1008) in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 232
- 试验地点
- 155
- 主要终点
- DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in European Union and United Kingdom
研究概览
简要总结
This was a randomized, double-blind study of rilzabrutinib in patients with persistent or chronic ITP, with an average platelet count of <30,000/μL (and no single platelet count >35,000/μL) on two counts at least 5 days apart in the 14 days before treatment begins. Patients received rilzabrutinib or placebo 400mg twice daily.
For each patient, the study lasted up to 60 weeks from the start of the Screening Period to the End of Study (EOS) visit. This included Screening (up to 4 weeks) through a 12 to 24-week Blinded Treatment Period followed by a 28-week Open-Label Period. Followed by a 4-week post dose follow-up.
For adult participants, the maximum duration of the long-term extension (LTE) period was 12 months from the date of the last adult participant to enter the LTE.
For pediatric participants, the maximum duration of the LTE period was 12 months from the date of the last pediatric participant to enter the LTE.
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
Double-Blind
入排标准
- 年龄范围
- 10 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female with primary ITP with duration of >6 months in pediatric participants aged 12 to <18 years (pediatric participants aged 10 to <12 years will be enrolled in the EU [EEA countries] only) and duration of >3 months in ages 18 years and above
- •Patients who had a response (achievement of platelet count ≥50,000/µL) to IVIg/anti-D or CSs that was not sustained and who have documented intolerance, insufficient response or any contra-indication to any appropriate courses of standard of care ITP therapy
- •An average of 2 platelet counts at least 5 days apart of <30,000/µL during the Screening period and no single platelet count >35,000/µL, within 14 days prior to the first dose of study drug.
- •- Pediatric patients must additionally be determined to need treatment for ITP as per clinical assessment by the Investigator.
- •Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.5 X 10^9/L, AST/ALT ≤1.5 x upper limit of normal [ULN], albumin ≥3 g/dL, total bilirubin ≤1.5 x ULN [unless the patient has documented Gilbert syndrome], glomerular filtration rate >50 [Cockcroft and Gault method for adult and Bedside Schwartz Equation for Pediatric participants])
- •Hemoglobin >9 g/dL within 1 week prior to Study Day 1
- •All contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
- •Patients must be able to provide written informed consent or informed assent with corresponding informed consent obtained from the patient's guardian and agree to the schedule of assessments
排除标准
- •Patients with secondary ITP
- •Pregnant or lactating women
- •History (within 5 years of Study Day 1) or current, active malignancy requiring or likely to require chemotherapeutic or surgical treatment during the study, with the exception of non melanoma skin cancer
- •Transfusion with blood, blood products, plasmapheresis, or use of any other rescue medications with intent to increase platelet count within 14 days before Study Day 1
- •Change in CS and/or TPO-RA dose within 14 days prior to Study Day 1 (more than 10% variation from current doses)
- •Immunosuppressant drugs other than CSs within 5 times the elimination half-life of the drug or 14 days of Study Day 1, whichever is longer
- •Treatment with rituximab or splenectomy within the 3 months prior to Study Day 1
- •- Patients treated with rituximab will have normal B-cell counts prior to enrollment
- •Had received any investigational drug within the 30 days before receiving the first dose of study medication, or at least 5 times elimination half-life of the drug (whichever is longer); patient should not be using an investigational device at the time of dosing
- •Patients who previously received treatment with Bruton's Tyrosine Kinase (BTK) inhibitors (except rilzabrutinib) within 30 days before the first dose of study drug are not eligible
- •Patients who previously received rilzabrutinib at any time are not eligible
- •History of solid organ transplant
- •Myelodysplastic syndrome
- •Live vaccine within 28 days prior to Study Day 1 or plan to receive one during the study
- •Planned surgery in the time frame of the dosing period
研究组 & 干预措施
Rilzabrutinib
Patients receive rilzabrutinib 400mg orally twice daily for up to 24 weeks followed by 28 weeks of open label period
干预措施: Rilzabrutinib (Drug)
Placebo
Patients receive matching placebo 400mg orally twice daily for up to 24 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in European Union and United Kingdom
时间窗: Up to 24 weeks
Durable platelet response per guidance in European Union and United Kingdom was defined as platelet counts at or above 50,000/mcL for at least 8 out of the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy.
DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in Regions Except European Union and United Kingdom
时间窗: Up to 24 weeks
Durable platelet response per guidance in regions except European Union and United Kingdom was defined as platelet counts at or above 50,000/mcL for \>=two-thirds of at least 8 non-missing weekly scheduled platelet measurements during the last 12 weeks of the 24-week blinded treatment period in the absence of rescue therapy, provided that at least 2 non-missing weekly scheduled platelet measurements were at or above 50,000/mcL during the last 6 weeks of the 24-week blinded treatment period.
次要结局
- DB Period: Number of Weeks With Platelet Count >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy(Up to 24 weeks)
- DB Period: Number of Weeks With Platelet Counts >=30,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy(Up to 24 weeks)
- DB Period: Time to First Platelet Count of >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and Doubled From Baseline(Up to 24 weeks)
- DB Period: Percentage of Participants Who Required Rescue Therapy(Up to 24 weeks)
- DB Period: Change From Baseline on Item 10 (Physical Fatigue) of the Immune Thrombocytopenia-Patient Assessment Questionnaire (ITP-PAQ) in Adult Participants at Week 13(Baseline (Day 1) and Week 13)
- DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) Assessment in Adult Participants at Week 25 Per Guidance in European Union and United Kingdom(Baseline (Day 1) and Week 25)
- DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale Assessment in Adolescent Participants at Week 25 Per Guidance in European Union and United Kingdom(Baseline (Day 1) and Week 25)
- DB-OL Period: Percentage of Participants With Stability of Response in Adult Participants(Up to 52 weeks)
- DB-OL Period: Percentage of Participants With Stability of Response in Adolescent Participants(Up to 52 weeks)
- DB Period: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs) and Bleeding Treatment-Emergent Adverse Events >=Grade 2(From first dose of study drug (Day 1) up to maximum DB exposure, up to 182 days (adults) and up to 175 days (adolescent))
- DB Period: Plasma Concentrations of Rilzabrutinib(Pre-dose at Weeks 1, 13 and 25 and 2 hours post-dose at Week 1 and 25 (adults); Pre-dose at Weeks 1, 13 and 25, 0.5, 2, 4 and 6 hours post-dose at Weeks 1 and 25 (adolescent))
- DB Period: Change From Baseline in the Symptoms, Bother and Activity Domains of the Immune Thrombocytopenia-Patient Assessment Questionnaire in Adult Participants(Baseline (Day 1) and Week 25)
- DB Period: Change From Baseline in Disease-Specific Quality Of Life as Measured by the Kids' Immune Thrombocytopenia Tools (ITP-KIT) Score in Adolescent Participants(Baseline (Day 1) and Week 25)