Study for Transfusionally Iron Overloaded Children, Adolescents and Adults Using FBS0701 (SSP-004184)
Condition: Iron Overload Due to Repeated Red Blood Cell Transfusions
MeSH terms: Iron Overload
Intervention: SSP-004184AQ
Intervention description: Long term extension study of 8-75 mg/kg/d of SSP-004184AQ (equivalent to 7-68 mg/kg/d free acid or "active" form)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 6 Years
Healthy volunteers: No

Summary:

      The purpose of this extension study is to evaluate SSP-004184AQ in patients with
      transfusional iron overload and to provide data on long term safety and efficacy.

      SSP-004184AQ is an iron chelator under development for chronic daily oral administration to
      patients with transfusional iron overload
    

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:

               1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or

               2. Surgically sterile, or

               3. 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).