A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Shire
- 入组人数
- 51
- 试验地点
- 9
- 主要终点
- Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks
研究概览
简要总结
The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in patients with β-thalassemia and other forms of anemia who experience iron overload - iron increases in the body as a result of regularly required blood transfusions. Patients who qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6 months) with a total study duration of up to 33 weeks. These patients will be eligible to participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be up to 96 weeks. The safety of patients will be monitored frequently during the study by physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart, each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the hospital for this study but will need to visit the outpatient clinic up to 28 times over the 96 week period. Patients currently taking an iron chelator will be required to stop for a total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be effective as an iron chelator.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone.
- •Willing to discontinue all existing iron chelation therapies throughout study period.
- •Serum ferritin greater than 500 ng/mL at Screening.
- •Baseline liver iron concentration and cardiac MRI T2* per protocol requirements.
- •Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.
- •Agrees to use an approved method of contraception throughout study period.
排除标准
- •As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study.
- •Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.)
- •Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator.
- •Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute.
- •Cardiac left ventricular ejection fraction outside of protocol requirements.
- •Known sensitivity to magnesium stearate, croscarmellose sodium or FBS
- •Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and <50% at Baseline testing by MRI
- •Alkaline phosphatase, AST or ALT outside of protocol requirements.
- •Liver Function Tests: ALT >5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening >200 IU/L
- •Use of any investigational agent within the 30 days prior to the Baseline testing.
研究组 & 干预措施
SPD602 (16mg)
干预措施: SPD602 (FBS0701, SSP-004184) (Drug)
SPD602 (32mg)
干预措施: SPD602 (FBS0701, SSP-004184) (Drug)
结局指标
主要结局
Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks
时间窗: Baseline and 96 weeks
LIC was determined by R2 Magnetic Resonance Imaging (MRI).
次要结局
- Maximum Plasma Concentration (Cmax) of SPD602(92 weeks)
- Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602(92 weeks)