A Phase 2, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Shire
- 入组人数
- 32
- 试验地点
- 12
- 主要终点
- Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
研究概览
简要总结
The purpose of this study is to evaluate SSP-004184AQ in patients with transfusional iron overload whose primary diagnosis is hereditary or congenital anemia.
SSP-004184AQ is an iron chelator under development for chronic daily oral administration to patients with transfusional iron overload.
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
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to sign the approved informed consent.
- •Age: 18-60 years old, inclusive, at Screening.
- •Subjects who have received more than 20 transfusions in their lifetime and who have transfusional iron overload requiring chronic treatment with an iron chelator. N.B.: Sickle Cell Disease subjects receiving regular exchange transfusions and iron overloaded subjects with thalassemia intermedia who are receiving regular transfusions (transfusion dependent thalassemia intermedia) are eligible.
- •Willing to discontinue all existing iron chelation therapies for a minimum period of one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the study and 1 week after last dose for a total of approximately 26 weeks.
- •Willing to fast two hours prior to and one hour after each dose.
- •Serum ferritin >500ng/mL at Screening.
- •Baseline liver iron concentration is greater than or equal to 5mg iron per g (equivalent dry weight, liver)determined by FerriScan® R2 MRI.
- •Mean of the previous three pre-transfusion hemoglobin concentrations is greater than or equal to 7.5g/dL.
- •Adult female subjects should be:
- •Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
- •Surgically sterile, or
- •Females of child-bearing potential must have a negative beta-HCG pregnancy test at the Screening Visit and a negative urine pregnancy test at the Baseline Visit.
- •Females of child-bearing potential must agree to abstain from sexual activity that could result in pregnancy or agree to use acceptable methods of contraception.
排除标准
- •As a result of medical review, physical examination, or Screening investigations, the Principal Investigator (PI) considers the subject unfit for the study.
- •Non-elective hospitalization within the 30 days prior to Baseline testing.
- •Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.
- •Iron overload from causes other than transfusional siderosis.
- •Evidence of severe renal insufficiency, eg, serum creatinine 1.5X above the upper limit of normal or proteinuria greater than 1 gm per day or a calculated glomerular filtration rate <60mL/min.
- •Severe iron overload including:
- •T2* MRI <10 ms
- •liver iron concentration by FerriScan R2 MRI >30mg/g liver (dw)
- •Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ.
- •Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at Screening.
- •Insufficient venous access that precludes prescribed blood draws for safety laboratory assessments.
- •ALT at Screening >200 IU/L.
- •Use of any investigational agent within the 30 days prior to the Baseline testing.
- •Pregnant or lactating females.
- •Cardiac left ventricular ejection fraction
- •Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or
- •<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).
研究组 & 干预措施
SPD602
50 mg/kg/day orally twice daily for 24 weeks
干预措施: SPD602 (Drug)
结局指标
主要结局
Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)
时间窗: Baseline, 12 and 24 weeks
The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI
时间窗: Baseline, 12 and 24 weeks
The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using FerriScan R2 standard procedures and used to determine LIC. A negative change from baseline indicates that LIC decreased. For participants who had a blood transfusion on the MRI exam date, the blood transfusion done immediately prior to the MRI exam date was included in the calculation of daily transfusion intake. Early Termination was within the protocol defined visit date +/- 14 days window and was mapped to next scheduled MRI visit for 3 participants.
次要结局
- Change From Baseline in LIC as Assessed by R2* MRI(Baseline, 12 and 24 weeks)
- Change From Baseline in Serum Ferritin(Baseline, 8 and 16 weeks)
- Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC(12 and 24 weeks)
- Change From Baseline in Cardiac T2* Relaxation Rate, an MRI Parameter Used to Estimate Cardiac Iron Load(Baseline, 12 and 24 weeks)
- Number of Participants Classified as a Responder by FerriScan R2 MRI Analysis of LIC Adjusted For Transfusional Iron Intake(12 and 24 weeks)
- Number of Participants Classified as a Responder by R2* MRI Analysis of LIC(12 and 24 weeks)
- Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI(Baseline, 12 and 24 weeks)
- Number of Participants Classified as a Responder by R2* MRI Analysis of LIC Adjusted For Transfusional Iron Intake(12 and 24 weeks)
- Number of Participants Classified as a Responder by Serum Ferritin(8 and 16 weeks)