Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study

A Randomized, Double-blind, Placebo-controlled, Phase II Study to Evaluate Efficacy and Safety of Deferasirox in Non-transfusion-dependent Thalassemia Patients With Iron Overload

CICL670A2209: This study will evaluate the safety and efficacy of deferasirox in non-transfusion dependent thalassemia patients with iron overload. Patients will be treated either with active treatment (deferasirox) or placebo for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study with the active treatment (deferasirox) in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the liver will be evaluated using magnetic resonance imaging (MRI) assessments.

CICL670A2209E1: A one-year open-label extension to a randomized, double-blind, placebo-controlled, phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload (Thalassa).

Core Inclusion Criteria:

• Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
• Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
• Serum ferritin >300 ng/mL at screening

Core Exclusion Criteria:

• Hemoglobin S (HbS)-variants of thalassemia syndromes
• Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded
• Any blood transfusion 6 months prior to study start
• Creatinine clearance ≤ 60 mL/min at screening
• Serum creatinine above the upper limit of normal at both screening visits
• Significant proteinuria as indicated by a urine protein/urine creatinine ratio > 1.0 mg/mg
• Alanine aminotransferase (ALT) of > 5 x the upper limit of normal at both screening visits
• Concomitant therapy with hydroxyurea, erythropoietin, butyrate
• History of deferasirox treatment
• Pediatric patients: a patient's weight of below 20 kg

Extension Inclusion Criteria:

• Patients who completed the core CICL670A2209 clinical trial
• Written informed consent obtained prior entry to one year extension study CICL670A2209

Extension Exclusion Criteria:

• Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and > ULN who did not improve after drug interruption or dose reduction in the core study
• Patients with a continuous increase in ALT greater than 2 times the baseline value and > 5 times ULN who did not improve after drug interruption or dose reduction in the core study
• Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study
• Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)

Other protocol-defined inclusion/exclusion criteria may apply