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

This is an interventional treatment trial for Iron Overload Due to Repeated Red Blood Cell Transfusions Read More

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).