Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload
Condition: Transfusional Iron Overload; Beta-thalassemia
MeSH terms: Thalassemia; beta-Thalassemia; Iron Overload
Intervention: SPD602 (FBS0701, SSP-004184)
Intervention description: Oral FBS0701 taken one time daily for up to 96 weeks.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: No
Keywords: Beta-thalassemia; Sickle cell anemia; Transfusional iron overload; Iron overload; Iron chelation

Summary:

      The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new
      oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a
      medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in
      patients with β-thalassemia and other forms of anemia who experience iron overload - iron
      increases in the body as a result of regularly required blood transfusions. Patients who
      qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6
      months) with a total study duration of up to 33 weeks. These patients will be eligible to
      participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be
      up to 96 weeks. The safety of patients will be monitored frequently during the study by
      physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart,
      each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the
      hospital for this study but will need to visit the outpatient clinic up to 28 times over the
      96 week period. Patients currently taking an iron chelator will be required to stop for a
      total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be
      effective as an iron chelator.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Transfusional iron overload due to: hereditary anemias such as sickle cell disease,
             β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic
             Syndrome and other forms of bone marrow failure. Patients must also be
             transfusion-dependent and require chronic treatment with deferoxamine, deferasirox,
             and/or deferiprone.

          -  Willing to discontinue all existing iron chelation therapies throughout study period.

          -  Serum ferritin greater than 500 ng/mL at Screening.

          -  Baseline liver iron concentration and cardiac MRI T2* per protocol requirements.

          -  Mean of the previous three pre-transfusion hemoglobin concentrations greater than or
             equal to 7.5 g/dL.

          -  Agrees to use an approved method of contraception throughout study period.

        Exclusion Criteria:

          -  As a result of medical review, physical examination or Screening investigations, the
             Principal Investigator considers the patient unfit for the study.

          -  Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients
             with sickle cell anemia who are admitted to the hospital for management of sickle
             crisis pain whose uncomplicated hospital course was four days or less and who, 14 days
             prior to Baseline testing, have returned to their previous health status are
             acceptable.)

          -  Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic,
             renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin
             disorder as determined by the Investigator.

          -  Evidence of significant renal insufficiency; possible examples include: serum
             creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or
             calculated creatinine clearance of less than 60 mL/minute.

          -  Cardiac left ventricular ejection fraction outside of protocol requirements.

          -  Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701.

          -  Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at
             Screening and <50% at Baseline testing by MRI

          -  Alkaline phosphatase, AST or ALT outside of protocol requirements.

          -  Liver Function Tests: ALT >5 times the local upper limit of normal on two occasions in
             the previous 12 months or ALT at Screening >200 IU/L

          -  Use of any investigational agent within the 30 days prior to the Baseline testing.