Efficacy/Safety Study of Deferiprone Compared to Deferasirox in Paediatric Patients
Condition: Chronic Iron Overload
MeSH terms: Hemoglobinopathies; Iron Overload
Intervention: Deferiprone; Deferasirox
Intervention description: Deferiprone 80 mg/mL oral solution; Deferasirox is used at the following dosage strengths: 125 mg, 250 mg and 500 mg
Intervention MeSH terms: Deferasirox; Deferiprone
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 435.0
Sex: All
Minimum age: 1 Month
Maximum age: 17 Years
Healthy volunteers: No
Keywords: chronic iron overload; hereditary haemoglobinopathy; beta thalassaemia major; chelating agents; deferiprone; deferasirox; children; paediatrics

Summary:

      Multicentre, randomised, open label, non-inferiority active-controlled trial to evaluate
      efficacy and safety of a 12-months treatment with deferiprone (DFP) at dose of 75-100
      mg/kg/day versus deferasirox (DFX) at dose of 20-40 mg/kg/day in paediatric patients (1 month
      < 18 years old) affected by hereditary haemoglobinopathies and requiring frequent
      transfusions and chelation.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients of both genders aged from 1 month up to less than 18 years at the time of
             enrolment

          -  Patients affected by any hereditary haemoglobinopathy requiring chronic transfusion
             therapy and chelation, including but not limited to thalassemia syndromes and sickle
             cell disease

          -  Patients on current treatment with deferoxamine (DFO) or DFX or DFP in a chronic
             transfusion program receiving at least 150 mL/kg/year of packed red blood cells
             (corresponding approximately to 12 transfusions);

          -  For patients naïve to chelation treatment: patients that have received at least 150
             mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a
             chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL;

          -  Until availability of results from the PK Study (Study DEEP-1, EudraCT n.
             2012-000658-67) for patients aged from 1 month to less than 6 years: known intolerance
             or contraindication to DFO;

          -  Written informed consent and patient's informed assent, relating to his/her
             comprehension abilities and level of maturity

        Exclusion Criteria:

          -  Patients with intolerance or known contraindication to either DFP or DFX

          -  Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at
             screening

          -  Platelet count <100.000/mm3 during the run-in phase

          -  Absolute neutrophils count <1.500/mm3 during the run-in phase

          -  Hb levels lower than 8g/dL during the run-in phase

          -  Evidence of abnormal liver function

          -  Iron overload from causes other than transfusional haemosiderosis

          -  Severe heart dysfunction secondary to iron overload

          -  Serum creatinine level > ULN (Upper Limit of Normal) for age during the run-in phase

          -  History of significant medical or psychiatric disorder

          -  The patient has received another investigational drug within 30 days prior to this
             clinical trial

          -  Fever and other signs/symptoms of infection in the 10 days before baseline assessment

          -  Concomitant use of trivalent cation-dependent medicinal products such as
             aluminium-based antacids

          -  Positive test for β-HCG (Human chorionic gonadotropin) and lactating female patients