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

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.

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).