A Randomized, Comparative, Open Label Phase III Trial on Efficacy & Safety of Long-term Treatment With ICL670 Compared to Deferoxamine in Beta-thalassemia Patients With Transfusional Hemosiderosis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 595
- 试验地点
- 7
- 主要终点
- Demonstrate non-inferiority to deferoxamine in its effects on liver iron content (LIC)
研究概览
简要总结
The purpose of this study is to deterimine if the new orally active iron chelator, ICL670, is as effective and as safe as deferoxamine in preventing accumulation of iron in the body while a patient is undergoing repeated blood transfusions.
详细描述
Patients who require repeated blood transfusions to live accumulate iron in the body as blood cells contain iron and there is no natural body mechanism to eliminate it. After a while the iron levels get high enough to be toxic to the body. The current therapy of choice is deferoxamine, which does a good job of removing excess iron, but is difficult to administer. Deferoxamine requires subcutaneous (under the skin) infusions over 4 to 8 hours nightly 3 to 7 nights per week. In addition to the need to wear an infusion pump nightly, adverse reactions around the site of the injection are frequent.
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
- None
入排标准
- 年龄范围
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Beta-thalassemia patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
- •Liver iron content greater than 2 mg iron/g dw as measured by liver biopsy
- •Need for regular transfusions 8 or more times per year
排除标准
- •Non-transfusional iron overload or transfusion-dependent anemias other than beta-thalassemia.
- •Documented toxicity to deferoxamine
- •Elevated liver enzymes in the year preceeding enrollment
- •Active hepatitis B or hepatitis C
- •HIV seropositivity
- •Elevated serum creatinine or significant proteinuria
- •History of nephrotic syndrome
- •Uncontrolled systemic hypertension
- •Fever and other signs/symptoms of infection within 10 days prior to start of the study
- •Presence of clinically relevant cataract or previous history of clinically relevant ocular toxicity related to iron chelation
- •Second or third degree AV block, clinically relevant Q-T interval prolongation, or patients requiring digoxin or other drugs that prolong the Q-T interval
- •Diseases (cardiovascular, renal, hepatic, etc.)that would prevent the patient from undergoing any of the treatment options
- •Psychiatric or additive disorders that would prevent the patient from giving informed consent
- •History of drug or alcohol abuse within the 12 months prior to the study
- •Pregnant or breast feeding patients
- •Patients treated with systemic investigational drugs within 4 weeks or topical investigational drugs within 7 days before the start of the study
- •Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as gastrointestinal disease or major surgery, renal disease, difficulty voiding or urinary obstruction, or impaired pancreatic function.
- •Non-compliant or unreliable patients.
- •Patients unable to undergo any study procedures such as the hearing or eye tests, or the liver echocardiography.
- •Inability to undergo a liver biopsy.
- •Patients that would need a dose of ICL670 less than 125 mg per day.
研究组 & 干预措施
ICL670
干预措施: ICL670 (Drug)
Deferoxamine
干预措施: deferoxamine (Drug)
结局指标
主要结局
Demonstrate non-inferiority to deferoxamine in its effects on liver iron content (LIC)
次要结局
- Evaluate tolerability profile
- Estimate absolute and relative change of LIC and Total body iron excretion
- Evaluation relationship between LIC and potential surrogate markers
- Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variable