A Single Arm, Open-label, Long-term Efficacy and Safety Study of Romiplostim in Thrombocytopenic Pediatric Subjects With Immune Thrombocytopenia (ITP)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 203
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Developed Collagen After Exposure to Romiplostim
研究概览
简要总结
This is a phase 3b single arm, open label, multicenter study describing the percentage of time pediatric participants with ITP have a platelet response while receiving romiplostim, defined as a platelet count ≥ 50 x 10^9/L in the absence of ITP rescue medications for the past 4 weeks.
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
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of primary ITP according to The American Society of Hematology (ASH) Guidelines at least 6 months before screening, regardless of splenectomy status
- •Age ≥ 1 year and < 18 years of age
- •Refractory to prior ITP therapy, relapsed after at prior ITP therapy, or be ineligible for other therapies. Examples of prior therapy include: corticosteroids, intravenous Immunoglobulin (IVIG), anti-D immunoglobulin, platelet transfusions.
- •Platelet count ≤ 30 x10^9/L or is experiencing uncontrolled bleeding
- •Has provided informed consent before any study-specific procedure;
- •Adequate hematologic, renal, and liver function during screening:
- •Hemoglobin > 10.0 g/dL
- •Serum creatinine ≤ 1.5 x the upper limit of normal (ULN)
- •Total serum bilirubin ≤ 1.5 x the ULN
- •Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x the ULN
- •For the EU, Switzerland and Turkey protocol supplement, subject must agree to a scheduled bone marrow biopsy and aspirate at Year 1 or Year 2 following romiplostim treatment and any unscheduled biopsies if clinically indicated
- •For the EU, Switzerland and Turkey protocol supplement, a reticulin grade of 0, 1, 2, or 3 according to the modified Bauermeister grading scale, as assessed by central laboratory from a bone marrow biopsy performed within 1 year prior to planned first dose of romiplostim or consent to a pre-treatment bone marrow biopsy and aspirate prior to planned first dose of romiplostim
排除标准
- •History of a bone marrow stem cell disorder (Any abnormal bone marrow findings other than those typical of ITP must be approved by Amgen before a subject may be enrolled)
- •Prior bone marrow transplant or peripheral blood progenitor cell transplant
- •Active or prior malignancy except non-melanoma skin cancers within the last 5 years
- •History of myelodysplastic syndrome
- •History of bleeding diathesis
- •History of congenital thrombocytopenia
- •History of Hepatitis B, Hepatitis C or human immunodeficiency virus (HIV)
- •History of systemic lupus erythematosus, Evans syndrome, or autoimmune neutropenia
- •History of antiphospholipid antibody syndrome or known positive for lupus anticoagulant
- •History of disseminated intravascular coagulation, hemolytic uremic syndrome, or thrombotic thrombocytopenic purpura
- •History of venous thromboembolism or thrombotic events
- •Previous use of romiplostim or previous use of eltrombopag within 4 weeks of enrollment
- •Previous use of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), recombinant human thrombopoietin (rHuTPO) or any other platelet producing agent
- •Rituximab (for any indication) or 6-mercaptopurine within 8 weeks of enrollment, or anticipated use at any time during the study
- •Splenectomy within 4 weeks of the screening visit
- •Alkylating agents within 8 weeks before the screening visit or anticipated use during the time of the proposed study
- •Vaccinations known to decrease platelet counts within 8 weeks before the screening visit
- •Currently enrolled in another investigational device or drug study, or less than 30 days since ending investigational study
- •Will have investigational procedures while enrolled on study
- •Female subject of child bearing potential (defined as having first menses) not willing to use, in combination with her partner highly effective methods of birth control during treatment and for 1 month after the end of treatment
- •Subject is pregnant or breast feeding, or might become pregnant within 1 month after the end of treatment
- •Subject has known hypersensitivity to any recombinant Escherichia coli derived product (eg, Infergen®, Neupogen®, somatropin, and Actimmune®)
- •Has previously enrolled into this study
- •Will not be available for protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge
- •Any kind of disorder that, may compromise the subject to give written informed consent and/or to comply with all required study procedures
研究组 & 干预措施
Romiplostim
Participants received romiplostim administered weekly by subcutaneous injection for up to 3 years. The starting dose was 1 µg/kg titrated in 1 µg/kg increments up to a maximum of 10 µg/kg to reach a target platelet count ≥ 50 x 10⁹/L.
干预措施: Romiplostim (Drug)
结局指标
主要结局
Percentage of Participants Who Developed Collagen After Exposure to Romiplostim
时间窗: Year 1 (Cohort 1) and year 2 (Cohort 2)
The percentage of participants who developed collagen as evidenced by trichrome staining, defined as a Grade 4 on the modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining)
Percentage of Participants With Increased Modified Bauermeister Grade
时间窗: Baseline, year 1 (Cohort 1) and year 2 (Cohort 2)
The percentage of participants with an increased modified Bauermeister grade defined as an increase by ≥ 2 severity grades or an increase to grade 4 (i.e., grade 0 to 2-4, grade 1 to 3-4, grade 2 to 4, or grade 3 to 4 over baseline). The modified Bauermeister grading scale: Grade 0: No reticulin fibers demonstrable Grade 1: Occasional fine individual fibers and foci of a fine fiber network Grade 2: Fine fiber network throughout most of the section; no coarse fibers Grade 3: Diffuse fiber network with scattered thick coarse fibers but no mature collagen (negative to trichrome staining) Grade 4: Diffuse, often course fiber network with areas of collagenization (positive trichrome staining) Participants without an evaluable baseline result were assumed to have a baseline modified Bauermeister score of 0.
Percentage of Time With a Platelet Response During the First 6 Months of Treatment
时间窗: Week 2 to Month 6, platelet response was assessed every week.
Platelet response was defined as a platelet count of ≥ 50 x 10⁹/L with no rescue medication use for ITP in the past 4 weeks. Monthly platelet response was calculated based on the median platelet count during each month. For each participant, the percentage of time with platelet response during the first 6 months was calculated as the number of months a platelet response was observed divided by the total number of months response was assessed.
Percentage of Participants Who Developed Bone Marrow Abnormalities
时间窗: Year 1 (Cohort 1) and year 2 (Cohort 2)
The percentage of participants with bone marrow abnormalities (eg, myelodysplastic syndrome, monosomy 7) based on analysis of bone marrow biopsy and aspirate samples using cytogenetics and fluorescence in situ hybridization.
次要结局
- Percentage of Time With a Platelet Response During the Overall Treatment Period(From week 2 to the end of the treatment period, 36 months)
- Percentage of Time With an Increase in Platelet Count ≥ 20 x 10⁹ Cells/L Above Baseline(Baseline and from week 2 to month 36)
- Number of Participants Reporting Use of Rescue Medications for ITP During the Treatment Period(From first dose of romiplostim to the end of the treatment period, 36 months)
- Number of Participants Who Developed Anti-Romiplostim or Anti-Thrombopoietin Neutralizing Antibodies(Week 12, week 52 and every 24 weeks thereafter up to month 36)
- Number of Participants With Adverse Events(SAEs were collected from Screening through end-of-study follow-up (up to 38 months). Nonserious AEs were collected from first to last dose of study drug during the treatment period (up to 36 months).)
- Percentage of Participants Who Developed Increased Reticulin(Baseline, year 1 (Cohort 1) and year 2 (Cohort 2))