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

A Phase 2, 24 Week, Open Label, Multi-Center Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of SSP-004184 (SPD602) 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.

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).