safety, efficacy and pharmacokinetics of an oral iron chelator given for a year to pediatric patients with iron overload

Conditions: Transfusional Iron Overload; Beta-Thalassemia

Summary: this is an open-label study to assess the pharmacokinetics, safety, efficacy and tolerability of ssp-004184aq. the study consists of two phases: the pharmacokinetic phase, using a single 16 mg/kg dose of ssp-004184aq; and the chronic dosing phase, during which patients will receive an additional 48 weeks of ssp-004184aq dosing. two age groups will be studied: 6-\<12, and 12-\<18 years old. the study is designed to initially assess the pharmacokinetics and safety of ssp-004184aq in older children (adolescents, 12-\<18 years old) and then if deemed safe, in younger children (6-\<12 years old).

pharmacokinetic phase: patients will receive a single 16 mg/kg dose of ssp-004184aq in capsule form. chronic dosing phase: patients will receive ssp-004184aq capsules daily for 48 weeks. doses may range from 8-60 mg/kg/d.

Eligibility criteria:
inclusion criteria * parents willing and able to sign the approved informed consent for their children and subjects between the ages of 6 and \<18 years willing and able to provide their assent (based on institutional guidelines). * able to swallow whole capsules. * age \>6 and \<18 years. * transfusion-dependent subjects who have transfusional iron overload requiring chronic treatment with deferoxamine, deferasirox, or deferiprone. a transfusion dependent subject is defined in this study as one with a minimum transfusion history totaling more than 20 units of packed red blood cells or a calculated iron load based on transfusion history of 200mg/kg and a transfusion requirement of 7 or more transfusions per year; or, in subjects with sickle cell anemia, be iron overloaded but can be receiving transfusion exchange therapy in lieu of transfusions. * in the opinion of the investigator (and in consultation with the subject's parents), the subject is able to discontinue all existing iron chelation therapies for a minimum period of 1-5 days prior first dose of ssp-004184aq, for the initial pharmacokinetic period of 8 days (if applicable), and for up to 49 weeks if continuing into the chronic dosing phase. * subjects able to have an mri must have: 1. liver iron concentration \>2 and \<30mg/g (dry weight, liver) by ferriscan® r2 2. cardiac mri t2\* \>10ms (note: subjects not able to have an mri will be considered iron overloaded on the basis of serum ferritin only.) * serum ferritin \>500ng/ml at screening. * mean of the previous 3 pre-transfusion hemoglobin concentrations greater than or equal to 7.5g/dl. * if appropriate, depending on age, female subjects of child-bearing potential need to use a medically acceptable method for birth control from screening until 30 days after the last dose of the study drug. females of child-bearing potential must have a negative serum 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 (including height and weight) or screening investigations, the principal investigator considers the subject unfit for the study. * iron overload from causes other than transfusional hemosiderosis. * severe cardiac dysfunction. * non-elective hospitalization within the 30 days prior to baseline testing. * evidence of clinically significant oral, cardiovascular, gastrointestinal, hepatic, biliary, renal, endocrine, pulmonary, neurologic, psychiatric, or skin disorder that contra-indicates dosing with ssp-004184aq. * evidence of significant renal insufficiency, eg, serum creatinine above the upper limit of normal or proteinuria greater than 1 gm per day. * known sensitivity to any ingredient in the ssp-004184aq formulation. * platelet count below 100,000/µl or absolute neutrophil count less than 1500/mm3 at screening. * alt \>180 iu/l at screening. * use of any investigational agent within the 30 days prior to baseline testing. * pregnant or lactating females. * cardiac left ventricular ejection fraction a) below the locally determined normal range in the 12 months prior to screening by echocardiography or mri or \<50% at baseline testing by mri (echocardiograph is acceptable for lvef if mri information is not available).

Keywords: beta-thalassemia sickle cell anemia transfusional iron overload iron overload iron chelation