Intervention: Deferitazole
Trial phase: Phase 2
SMILES: COCCOCCOCCOc1cccc(C2=N[C@@](C)(C(=O)O)CS2)c1O
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 30
Group description: Participants received SSP-004184AQ (magnesium salt of free acid or active form, that is, SSP-004184 [SPD602, FBS0701]) capsules orally at a total daily dose of 8-75 mg/kg/day (equivalent to SSP-004184 7-68 mg/kg/day) either once daily or twice daily at the discretion of investigator for up to a maximum of 3 years or until the sponsor decided to stop the study.
Eligibility criteria:
Inclusion Criteria:

Subjects and/or parents willing and able to sign the approved informed consent/and assent (based on institutional guidelines).
An understanding, ability, and willingness to fully comply with study procedures and restrictions.
Has either completed a previous SSP-004184AQ study or prematurely discontinued from (with agreement from the Investigator and Shire physician) from one of the SSP-004184AQ studies.

If applicable, female subjects should be either:

Post-menopausal (12 consecutive months of spontaneous amenorrhea), or
Surgically sterile, or

Females of child-bearing potential must have a negative urine pregnancy test at the Qualification and Enrollment Visit prior to dosing on Day 1. 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.

For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ:

Willing to discontinue all existing iron chelation therapies for a minimum period of 1 to 5 days prior to first dose of SSP-004184AQ.

(Note: This inclusion criterion is also applicable for subjects that were receiving chelators other than SSP-004184AQ in their feeder protocol.)

Serum ferritin greater than 500 ng/mL at the Qualification and Enrollment Visit.
Liver iron concentration (LIC) greater than or equal to 2.0 mg iron per g (equivalent dry weight, liver) determined by FerriScan® R2 MRI at the Qualification and Enrollment Visit (Day -28 to Day -8).

(Note: Younger subjects for whom MRI is not feasible will be considered iron overloaded on the basis of serum ferritin only.) - Mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL.

Exclusion:

Unwilling to remain off all other existing chelation therapies during SSP-004184AQ dosing and for up to 24 hours from last dose.
A history of non-compliance in a prior FerroKin/Shire-sponsored SSP-004184AQ study (excluding dose suspensions that were medically warranted).
Cardiac MRI T2* less than 10.0 milliseconds at the Qualification and Enrollment Visit.
Cardiac left ventricular ejection fraction less than 50% at the Qualification and Enrollment Visit by MRI or below the locally determined normal range by echocardiography if MRI information is not available.
Evidence of clinically relevant oral, cardiovascular, gastrointestinal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow, dermatologic, hepatic, biliary, or renal dysfunction where, in the opinion of the Investigator or the Shire Study Physician, treatment with SSP-004184AQ is relatively contraindicated.
Platelet count below 100,000/µL or absolute neutrophil count less than 1500/mm3 at the Qualification and Enrollment Visit.
Known sensitivity to any ingredient in the SSP-004184AQ formulation.
Pregnant or lactating females.

For subjects that did not transition directly from their feeder protocol and have initiated treatment with a chelator other than SSP-004184AQ:

In younger subjects for whom MRI is not feasible, evidence of severe cardiac dysfunction, as assessed by the Investigator.
Non-elective hospitalization within the 30 days prior to receiving the first dose of SSP 004184AQ.
For subjects greater than or equal to 18 years old: ALT greater than 200 IU/L at the Qualification and Enrollment Visit.

OR For subjects less than 18 years old: ALT greater than 180 IU/L at the Qualification and Enrollment Visit.

- For subjects greater than or equal to 18 years old: 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 less than 40 mL/min.

OR For subjects less than 18 years old: Evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day.

Use of any investigational agent within the 30 days prior to receiving the first dose of SSP-004184AQ.
Cardiac left ventricular ejection fraction below the locally determined normal range in the 12 months prior to Screening by echocardiography or MRI or less than 50% at Baseline testing by MRI (Echocardiograph is acceptable for LVEF if MRI information is not available).