A Randomized, Double-blind, Placebo-controlled, Phase II Study to Evaluate Efficacy and Safety of Deferasirox in Non-transfusion-dependent Thalassemia Patients With Iron Overload
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 4
- 主要终点
- Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
研究概览
简要总结
CICL670A2209: This study will evaluate the safety and efficacy of deferasirox in non-transfusion dependent thalassemia patients with iron overload. Patients will be treated either with active treatment (deferasirox) or placebo for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study with the active treatment (deferasirox) in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the liver will be evaluated using magnetic resonance imaging (MRI) assessments.
CICL670A2209E1: A one-year open-label extension to a randomized, double-blind, placebo-controlled, phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload (Thalassa).
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
- Triple (Participant, Care Provider, Investigator)
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 or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
- •Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
- •Serum ferritin >300 ng/mL at screening
排除标准
- •Hemoglobin S (HbS)-variants of thalassemia syndromes
- •Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded
- •Any blood transfusion 6 months prior to study start
- •Creatinine clearance ≤ 60 mL/min at screening
- •Serum creatinine above the upper limit of normal at both screening visits
- •Significant proteinuria as indicated by a urine protein/urine creatinine ratio > 1.0 mg/mg
- •Alanine aminotransferase (ALT) of > 5 x the upper limit of normal at both screening visits
- •Concomitant therapy with hydroxyurea, erythropoietin, butyrate
- •History of deferasirox treatment
- •Pediatric patients: a patient's weight of below 20 kg
- •Extension Inclusion Criteria:
- •Patients who completed the core CICL670A2209 clinical trial
- •Written informed consent obtained prior entry to one year extension study CICL670A2209
- •Extension Exclusion Criteria:
- •Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and > ULN who did not improve after drug interruption or dose reduction in the core study
- •Patients with a continuous increase in ALT greater than 2 times the baseline value and > 5 times ULN who did not improve after drug interruption or dose reduction in the core study
- •Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study
- •Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)
- •Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
5 mg/kg/day deferasirox
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: deferasirox (Drug)
5 mg/kg/day deferasirox
Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: placebo (Drug)
10 mg/kg/day deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: deferasirox (Drug)
10 mg/kg/day deferasirox
Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: placebo (Drug)
5 mg/kg/day placebo
Placebo tablet matching 5 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: placebo (Drug)
10 mg/kg/day placebo
Placebo tablet matching 10 mg/kg/day orally in the morning each day for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.
干预措施: placebo (Drug)
结局指标
主要结局
Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
时间窗: Baseline, Week 52
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.
Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study
时间窗: Core Baseline to End of Extension Study (up to 24 months)
Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported.
次要结局
- Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24(Baseline, Week 24)
- Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter(Baseline, (Day 286 to End of Study [Day 365]))
- Core Study: Change in Serum Ferritin Between Baseline and Second Quarter(Baseline, (Day 106 to Day 195))
- Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe(52 Weeks)
- Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24(Baseline, Week 24, Week 52)
- Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)(Baseline, 52 weeks)
- Core Study: Change From Baseline in Hemoglobin at Month 12(Baseline, Month 12)
- Core Study: Change From Baseline in Transferrin Saturation at Month 12(Baseline, Month 12)
- Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52(Baseline, Week 52)
- Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results(52 Weeks)
- Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure(Baseline, 52 Weeks)
- Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure(Baseline, 52 Weeks)
- Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate(Baseline, 52 Weeks)
- Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter(Core Baseline, Eighth Quarter (last 3 months of the study))
- Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24(Core Baseline, Month 24)
- Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)(Core Baseline, Month 24)
- Extension Study: Change From Baseline in Hemoglobin at Month 24(Core Baseline, Month 24)
- Extension Study: Change From Baseline in Transferrin Saturation at Month 24(Core Baseline, Month 24)