Safety and Pharmacodynamic Study of an Oral Iron Chelator Given for 6 Months to Patients With Iron Overload

Study Overview
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Brief Summary
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The purpose of this research study is to evaluate the safety of two doses of FBS0701, a new oral iron chelator, and its effectiveness in clearing iron from the liver. FBS0701 is a medication taken by mouth that causes the body to get rid of iron. Iron chelators are used in patients with β-thalassemia and other forms of anemia who experience iron overload - iron increases in the body as a result of regularly required blood transfusions. Patients who qualify will be randomized to receive one of two doses of FBS0701 for up to 24 weeks (6 months) with a total study duration of up to 33 weeks. These patients will be eligible to participate in a dosing extension for up to 72 weeks. The maximum duration of dosing will be up to 96 weeks. The safety of patients will be monitored frequently during the study by physical exams, ECGs, and blood tests. To assess the amount of iron in the liver and heart, each patient must undergo 6 MRI scans during the study. Patients will not need to stay in the hospital for this study but will need to visit the outpatient clinic up to 28 times over the 96 week period. Patients currently taking an iron chelator will be required to stop for a total of up to 26 weeks. The results of this study will help to determine if FBS0701 may be effective as an iron chelator.

Official Title
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A Phase 2, 24 Week, Randomized, Open Label, Multi-Center Study to Assess the Safety, Tolerability, and Pharmacodynamics of FBS0701 in the Treatment of Chronic Iron Overload Requiring Chelation Therapy, With a 72 Week Dosing Extension

Conditions
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Transfusional Iron Overload, Beta-thalassemia

Intervention / Treatment
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* Drug: SPD602 (FBS0701, SSP-004184)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Transfusional iron overload due to: hereditary anemias such as sickle cell disease, β-thalassemia and Diamond-Blackfan anemia; acquired anemias such as Myelodysplastic Syndrome and other forms of bone marrow failure. Patients must also be transfusion-dependent and require chronic treatment with deferoxamine, deferasirox, and/or deferiprone. Willing to discontinue all existing iron chelation therapies throughout study period. Serum ferritin greater than 500 ng/mL at Screening. Baseline liver iron concentration and cardiac MRI T2* per protocol requirements. Mean of the previous three pre-transfusion hemoglobin concentrations greater than or equal to 7.5 g/dL. Agrees to use an approved method of contraception throughout study period. Exclusion Criteria: As a result of medical review, physical examination or Screening investigations, the Principal Investigator considers the patient unfit for the study. Non-elective hospitalization within the 30 days prior to Baseline testing. (Patients with sickle cell anemia who are admitted to the hospital for management of sickle crisis pain whose uncomplicated hospital course was four days or less and who, 14 days prior to Baseline testing, have returned to their previous health status are acceptable.) Evidence of clinically relevant oral, cardiovascular, gastrointestinal, hepatic, renal, endocrine, pulmonary, neurologic, psychiatric, immunologic, bone marrow or skin disorder as determined by the Investigator. Evidence of significant renal insufficiency; possible examples include: serum creatinine above the upper limit of normal, proteinuria greater than 2 gm per day or calculated creatinine clearance of less than 60 mL/minute. Cardiac left ventricular ejection fraction outside of protocol requirements. Known sensitivity to magnesium stearate, croscarmellose sodium or FBS0701. Platelet count below 100,000/µL and/or absolute neutrophil count less than 1500/mm3 at Screening and <50% at Baseline testing by MRI Alkaline phosphatase, AST or ALT outside of protocol requirements. Liver Function Tests: ALT >5 times the local upper limit of normal on two occasions in the previous 12 months or ALT at Screening >200 IU/L Use of any investigational agent within the 30 days prior to the Baseline testing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPD602 (16mg)<br> | Drug: SPD602 (FBS0701, SSP-004184)<br>* Oral FBS0701 taken one time daily for up to 96 weeks.<br>|
| Experimental: SPD602 (32mg)<br> | Drug: SPD602 (FBS0701, SSP-004184)<br>* Oral FBS0701 taken one time daily for up to 96 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Liver Iron Concentration (LIC) at 96 Weeks | LIC was determined by R2 Magnetic Resonance Imaging (MRI). | Baseline and 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Plasma Concentration (Cmax) of SPD602 | Cmax is a term that refers to the maximum (or peak) concentration that a drug achieves in the body after the drug has been administered. | 92 weeks | 
| Area Under The Steady-state Plasma Concentration-time Curve (AUC) of SPD602 | AUC can be used as a measure of drug exposure. It is derived from drug concentration and time so it gives a measure of how much and how long a drug stays in a body. | 92 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Beta-thalassemia, Sickle cell anemia, Transfusional iron overload, Iron overload, Iron chelation