Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study
Condition: Non-transfusion Dependent Thalassemia
MeSH terms: Thalassemia; Iron Overload
Intervention: deferasirox; placebo
Intervention description: Supplied as 125 mg, 250 mg and 500 mg tablets.; Supplied as matching 125 mg, 250 mg and 500 mg tablets.
Intervention MeSH terms: Deferasirox
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 166.0
Sex: All
Minimum age: 10 Years
Healthy volunteers: No
Keywords: Thalassemia; thalassemia intermedia; alpha-thalassemia; beta-thalassemia; deferasirox; iron overload; non-transfusion dependent

Summary:

      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).
    

Eligibility criteria:

        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