Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload

This is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of SSP-004184AQ. The study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of SSP-004184AQ; and the chronic dosing phase, during which patients will receive an additional 48 weeks of SSP-004184AQ dosing. Two age groups will be studied: 6-\<12, and 12-\<18 years old. The study is designed to initially assess the pharmacokinetics and safety of SSP-004184AQ in older children (adolescents, 12-\<18 years old) and then if deemed safe, in younger children (6-\<12 years old).

Pharmacokinetic Phase: Patients will receive a single 16 mg/kg dose of SSP-004184AQ in capsule form.

Chronic Dosing Phase: Patients will receive SSP-004184AQ capsules daily for 48 weeks. Doses may range from 8-60 mg/kg/d.

Eligibility Criteria:
Inclusion Criteria

* Parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and \<18 years willing and able to provide their assent (based on institutional guidelines).
* Able to swallow whole capsules.
* Age \>6 and \<18 years.
* Transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. A transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells OR a calculated iron load based on transfusion history of 200mg/kg AND a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions.
* In the opinion of the Investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of SSP-004184AQ, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase.
* Subjects able to have an MRI must have:

  1. liver iron concentration \>2 and \<30mg/g (dry weight, liver) by FerriScan® R2
  2. cardiac MRI T2\* \>10ms (Note: Subjects not able to have an MRI will be considered iron overloaded on the basis of serum ferritin only.)
* Serum ferritin \>500ng/mL at Screening.
* Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dL.
* If appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. Females of child-bearing potential must have a negative serum 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 (including height and weight) or Screening investigations, the Principal Investigator considers the subject unfit for the study.
* Iron overload from causes other than transfusional hemosiderosis.
* Severe cardiac dysfunction.
* Non-elective hospitalization within the 30 days prior to Baseline testing.
* Evidence of clinically significant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, or skin disorder that contra-indicates dosing with SSP-004184AQ.
* Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day.
* Known sensitivity to any ingredient in the SSP-004184AQ formulation.
* Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at Screening.
* ALT \>180 IU/L at Screening.
* Use of any investigational agent within the 30 days prior to Baseline testing.
* Pregnant or lactating females.
* Cardiac left ventricular ejection fraction a) Below the locally determined normal range in the 12 months prior to screening by echocardiography or MRI or \<50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI information is not available).