Safety, Efficacy and Pharmacokinetics of an Oral Iron Chelator Given for a Year to Pediatric Patients With Iron Overload
Condition: Transfusional Iron Overload; Beta-Thalassemia
MeSH terms: Thalassemia; beta-Thalassemia; Iron Overload
Intervention: SPD602
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 30.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Beta-Thalassemia; Sickle Cell Anemia; Transfusional iron overload; Iron Overload; Iron Chelation

Summary:

      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).
    

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).