Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy
Condition: Iron Overload Due to Repeated Red Blood Cell Transfusions
MeSH terms: Iron Overload
Intervention: SPD602
Intervention description: 50 mg/kg/day orally twice daily for 24 weeks
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate SSP-004184AQ in patients with transfusional iron
      overload whose primary diagnosis is hereditary or congenital anemia.

      SSP-004184AQ is an iron chelator under development for chronic daily oral administration to
      patients with transfusional iron overload.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Willing and able to sign the approved informed consent.

          -  Age: 18-60 years old, inclusive, at Screening.

          -  Subjects who have received more than 20 transfusions in their lifetime and who have
             transfusional iron overload requiring chronic treatment with an iron chelator. N.B.:
             Sickle Cell Disease subjects receiving regular exchange transfusions and iron
             overloaded subjects with thalassemia intermedia who are receiving regular transfusions
             (transfusion dependent thalassemia intermedia) are eligible.

          -  Willing to discontinue all existing iron chelation therapies for a minimum period of
             one to five days prior to first dose of SSP-004184AQ, the 24 week duration of the
             study and 1 week after last dose for a total of approximately 26 weeks.

          -  Willing to fast two hours prior to and one hour after each dose.

          -  Serum ferritin >500ng/mL at Screening.

          -  Baseline liver iron concentration is greater than or equal to 5mg iron per g
             (equivalent dry weight, liver)determined by FerriScan® R2 MRI.

          -  Mean of the previous three pre-transfusion hemoglobin concentrations is greater than
             or equal to 7.5g/dL.

          -  Adult female subjects should be:

               1. Post-menopausal (12 consecutive months of spontaneous amenorrhea), or

               2. Surgically sterile, or

               3. Females of child-bearing potential must have a negative 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, or Screening investigations, the
             Principal Investigator (PI) considers the subject unfit for the study.

          -  Non-elective hospitalization within the 30 days prior to Baseline testing.

          -  Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic,
             biliary, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone
             marrow, or skin disorder that contraindicates dosing with SSP-004184AQ.

          -  Iron overload from causes other than transfusional siderosis.

          -  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 <60mL/min.

          -  Severe iron overload including:

               1. T2* MRI <10 ms

               2. liver iron concentration by FerriScan R2 MRI >30mg/g liver (dw)

          -  Known sensitivity to magnesium stearate, croscarmellose sodium or SSP-004184AQ.

          -  Platelet count below 100,000/μL or absolute neutrophil count less than 1500/mm3 at
             Screening.

          -  Insufficient venous access that precludes prescribed blood draws for safety laboratory
             assessments.

          -  ALT at Screening >200 IU/L.

          -  Use of any investigational agent within the 30 days prior to the Baseline testing.

          -  Pregnant or lactating females.

          -  Cardiac left ventricular ejection fraction

               1. Below the locally determined normal range in the 12 months prior to Screening by
                  echocardiograph or MRI or

               2. <50% at Baseline testing by MRI (echocardiograph is acceptable for LVEF if MRI
                  information is not available).