Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload

• Safety and Tolerability based on clinical assessments (AEs, ECGs, Physical Exam, Clinical Laboratory tests) [ Time Frame: 96 weeks (24 weeks of dosing and up to a 72 week dosing extension) ] [ Designated as safety issue: Yes ]
• Changes in liver iron concentration by MRI [ Time Frame: up to 96 weeks (Baseline, week 12, week 24, week 48 and week 96.) ] [ Designated as safety issue: No ]
• Assess the safety and pharmacodynamic activity of FBS0701 when administered daily for up to 96 weeks [ Time Frame: up to 96 weeks ] [ Designated as safety issue: Yes ]

• Safety and Tolerability based on clinical assessments (AEs, ECGs, Physical Exam, Clinical Laboratory tests) [ Time Frame: 30 weeks (26 weeks of dosing and 4 weeks follow up) ] [ Designated as safety issue: Yes ]
• Changes in liver iron concentration by MRI [ Time Frame: up to 26 weeks (Baseline, week 12, week 24) ] [ Designated as safety issue: No ]

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.

• Transfusional Iron Overload
• Beta-thalassemia

• Experimental: SPD602 (16mg)
  Intervention: Drug: SPD602 (FBS0701, SSP-004184)
• Experimental: SPD602 (32mg)
  Intervention: Drug: SPD602 (FBS0701, SSP-004184)

• Neufeld EJ, Galanello R, Viprakasit V, Aydinok Y, Piga A, Harmatz P, Forni GL, Shah FT, Grace RF, Porter JB, Wood JC, Peppe J, Jones A, Rienhoff HY Jr. A phase 2 study of the safety, tolerability, and pharmacodynamics of FBS0701, a novel oral iron chelator, in transfusional iron overload. Blood. 2012 Apr 5;119(14):3263-8. Epub 2012 Jan 17.
• Rienhoff HY Jr, Viprakasit V, Tay L, Harmatz P, Vichinsky E, Chirnomas D, Kwiatkowski JL, Tapper A, Kramer W, Porter JB, Neufeld EJ. A phase 1 dose-escalation study: safety, tolerability, and pharmacokinetics of FBS0701, a novel oral iron chelator for the treatment of transfusional iron overload. Haematologica. 2011 Apr;96(4):521-5. Epub 2010 Dec 20.

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.