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

Phase 4

Terminated

Brief Summary: 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: The secondary endpoints that were originally planned for this study were not analyzed as the study ended prematurely.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Serum ferritin level < 1,000 μg/l	No chelation	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
Serum ferritin level ≥ 1,000 μg/l	Chelation	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
Serum ferritin level ≥ 1,000 μg/l	ICL670	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

Primary Outcome Measures

Name	Time	Method
Change in Serum Ferritin Values	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 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.
Change in Transferrin Saturation With Iron (TSI) Values	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	Mean percentage change from baseline in transferrin saturation with iron was summarized descriptively for all on-treatment study visits.
Change in Serum Total Iron-binding Capacity (TIBC)	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	Mean change from baseline in serum total iron-binding capacity was summarized descriptively for all on-treatment study visits.