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

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).