Pharmacokinetics of SSP-004184 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy

Inclusion Criteria:

• Willing and able to sign the approved informed consent.
• Age: 18-60 years old 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-004184, 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.
• Agrees to use an approved method of contraception from Screening and until 7 days after the last administration of the investigational product.

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 (eg, chronic cholecystitis), renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder that contraindicates dosing with SSP-004184.
• 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 <40mL/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-004184.
• 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.