Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients
Condition: Sickle Cell Disease; Iron Overload; Hemolytic Anemia
MeSH terms: Anemia, Sickle Cell; Anemia, Hemolytic; Iron Overload
Intervention: Deferasirox (ICL670); Deferoxamine (DFO)
Intervention description: Deferasirox was provided in 125 mg, 250 mg, and 500 mg dispersible tablets and was administered orally at an initial dose of 20 mg/kg/day.; Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg.
Intervention MeSH terms: Deferasirox; Deferoxamine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 212.0
Sex: All
Minimum age: 2 Years
Healthy volunteers: No
Keywords: Sickle Cell Disease; Iron Overload from Repeated Blood Transfusions; Iron Overload; Blood Transfusions

Summary:

      This study will examine the long-term safety and efficacy of Deferasirox in patients with
      sickle cell disease and iron overload from repeated blood transfusions.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age greater than or equal to 2 years

          -  Male or female patients with sickle cell disease (SS, SC, SD, Sβo or Sβ+ thalassemia)

          -  Iron overload from repeated blood transfusion, as defined by one of the following:

               1. For patients > 16 years old receiving simple transfusions: lifetime history of
                  receipt of at least 120 ml/kg or 30 adult units of packed red blood cells, OR

               2. For patients ≤ 16 years old receiving simple transfusions: lifetime history of
                  receipt of at least 120 ml/kg of packed red blood cells, OR

               3. For all patients receiving exchange transfusions in the absence of a previous
                  attempt to achieve negative iron balance: lifetime performance of at least 20
                  procedures, OR

               4. For all patients: liver iron content ≥ 7 mg Fe/g dry weight as measured by
                  biopsy, Magnetic Resonance Imaging (MRI), or magnetic susceptibility performed
                  within 3 months prior to entry into screening

          -  For entry into the screening period: serum ferritin of ≥ 1000 µg/mL on at least two
             occasions during the prior year obtained in the absence of concomitant infection.

          -  Body weight > 10 kg

          -  No known allergy or contraindication to the administration of deferoxamine

          -  Ability to comply with all study-related procedures, medications, and evaluations

          -  Sexually active pre-menopausal female patients must use double-barrier contraception,
             oral contraceptive plus barrier contraceptive, or must have undergone clinically
             documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal
             defined by amenorrhea for at least 12 months.

          -  Written informed consent by the patient or for pediatric patient's consent of the
             patient's legal guardian. The definition of the term 'pediatric' for enrollment and
             study conduct will be in accordance with the local legislation.

        Exclusion Criteria:

          -  Serum creatinine above the upper limit of normal

          -  Significant proteinuria

          -  History of nephrotic syndrome

          -  Alanine aminotransferase (ALT) ≥ 250 U/L at screening

          -  Clinical evidence of active hepatitis B or hepatitis C

          -  History of HIV

          -  Fever or other signs/symptoms of infection within 10 days prior to the screening visit

          -  Uncontrolled systemic hypertension

          -  History of Myocardial Infarction, Congestive Heart Failure or unstable cardiac disease
             not controlled by standard medical therapy

          -  Clinically relevant cataract or a previous history of clinically relevant ocular
             toxicity related to iron chelation

          -  Presence of a surgical or medical condition that might significantly alter the
             absorption, distribution, metabolism or excretion of any study drug

          -  History of drug or alcohol abuse within the 12 months prior to enrollment

          -  Pregnant or breast feeding patients

          -  Patients treated with systemic investigational drug within 4 weeks prior or with
             topical investigational drug 7 days prior to the screening visit

          -  Randomization in a previous clinical trial involving ICL670

        Other protocol-related inclusion / exclusion criteria may apply.