Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

Phase 2TerminatedNCT01604941

Shire32 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Iron Overload Due to Repeated Red Blood Cell Transfusions

Interventions

SPD602DRUG

50 mg/kg/day orally twice daily for 24 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 60 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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: 1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or 2. Surgically sterile, or 3. 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. Exclusion Criteria: * 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: 1. T2\* MRI \<10 ms 2. 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 1. Below the locally determined normal range in the 12 months prior to Screening by echocardiograph or MRI or 2. \<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).

Locations (12)

Children's Center for Cancer and Blood Diseases

Los Angeles, California, United States

Ann & Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Weill Cornell Medical College

New York, New York, United States

Outcomes

Primary Outcomes

Change From Baseline in Liver Iron Concentration (LIC) as Assessed by FerriScan R2 Magnetic Resonance Imaging (MRI)

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.

Time frame: Baseline, 12 and 24 weeks

Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by FerriScan R2 MRI

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.

Time frame: Baseline, 12 and 24 weeks

Secondary Outcomes

Change From Baseline in LIC as Assessed by R2* MRI

The efficacy of SPD602 was assessed by determining LIC. Abdominal MRI data were collected by using R2\* standard procedures (liver and pancreas) 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.

Time frame: Baseline, 12 and 24 weeks

Change From Baseline in LIC Adjusted by Transfusional Iron Intake And Assessed by R2* MRI

The efficacy of SPD602 was assessed by determining LIC and adjusting for transfusional iron intake. Abdominal MRI data were collected by using R2\* standard procedures (liver and pancreas) 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.

Data from ClinicalTrials.gov

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