Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients

Study Overview
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Brief Summary
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Evaluated Exjade efficacy and safety in patients with aplastic anemia and transfusion-dependent iron overload, undergoing treatment programs of immunosuppressive treatment (Cyclosporine A) , in comparison with a group of patients undergoing treatment programs of immunosuppressive treatment (Cyclosporine A) without chelation therapy.

Detailed Description
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The secondary endpoints that were originally planned for this study were not analyzed as the study ended prematurely.

Official Title
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Open-label Study of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients Undergoing Treatment Programs in Comparison With Control Group

Conditions
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Aplastic Anemia

Intervention / Treatment
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* Drug: ICL670
* Drug: Chelation
* Drug: No chelation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Main diagnosis: aplastic anemia Absence of severe and/or uncontrolled comorbidities Confirmed iron overload (serum ferritin ≥ 1000 mkg/L) Serum creatinine is not higher than the upper limit of normal for the given age Absence of severe proteinuria. Protein/Creatinine ratio should be < 0.5 mg/mg Liver enzymes are < 5 ULN Completion of a scheduled cycle of immunosuppressive treatment program, with no severe infectious or generalized hemorrhagic complications WHO (ECOG) performance status ≤ 2 Exclusion Criteria: No signed informed consent form Patient is under 18 years old Severe concomitant condition Severe infectious and generalized haemorrhagic complication following regular planned cycle of programmed immune suppressive treatment. History of increased sensitivity to active substance and any other ingredient of the medicinal product. Creatinine clearance (CC) < 60 ml/min and/or creatinine concentration in blood serum is 2 or more times higher than upper limit of age normal by results of 2 tests at Visits 1 and 2. Severe liver disorders (class C by Child-Pugh scale). Patients with aplastic anaemia in which chelator treatment will be ineffective due to rapid progression of the disease. Significant proteinuria basing on protein creatinine ratio > 1.0 mg/ml in urine sample from second urination at Visits 1 and 2 (or as an alternative in 2 of 3 urine samples at screening); Rare hereditary disorders related to galactose intolerance, severe deficit of lactase or glucose-galactose malabsorption; Pregnancy, lactation; Level of liver enzymes higher than 5 upper limits of age normal at Visits 1 and 2.

Ages Eligible for Study
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Minimum Age: 18 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: Serum ferritin level ≥ 1,000 μg/l<br>Transfusion-dependent adult patients with AA and serum ferritin ≥ 1000 mg/L on programmed immune suppressive treatment with cyclosporine A who were receiving chelation with Exjade (deferasirox) during the study | Drug: ICL670<br>* ICL670 was supplied in registered packages as 250mg or 500mg dispersible tablets.<br>* Other names: Deferasirox;Drug: Chelation<br>* Main group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment (immunosupressant - Cyclosporine A) and received chelation with ICL670 (deferasirox).<br>|
| Experimental: Serum ferritin level < 1,000 μg/l<br>Transfusion-dependent adult patients with AA and serum ferritin < 1,000 mg/L on programmed immune suppressive treatment with cyclosporine A who were not receiving the investigational product | Drug: No chelation<br>* Comparative group of patients with aplastic anemia and transfusion-dependent iron overload underwent treatment programs of standard immunosuppressive treatment ( immunosupressant -Cyclosporine A)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum Ferritin Values | Change from baseline was be summarized descriptively for all on-treatment study visits. Changes to the planned statistical analysis were related to significant withdrawal of patients from the Per-Protocol Analysis Set due to a large number of patients who discontinued the study (lack of assessments of iron exchange parameters at visits) and deviations from the Protocol affecting the assessment of efficacy parameters. Because of that, the additional efficacy analysis in the Per-Protocol Analysis Set was not performed. | Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52 | 
| Change in Transferrin Saturation With Iron (TSI) Values | Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits. | Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52 | 
| Change in Serum Total Iron-binding Capacity (TIBC) | Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits. | Screening, Week (Wk) 4, Wk 8, Wk 12, Wk 16, Wk 20, Wk 24, Wk 28, Wk 32, Wk 36, Wk 40, Wk 44, Wk 48, Wk 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aplastic anemia, deferasirox, ICL670, renal function, transfusion-dependent iron overload, immunosuppressive treatment, Cyclosporine A, unosuppressive treatment without chelation therapy