Study of Deferasirox Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Open-label, Multi-center, Phase II Study to Evaluate the Safety and Efficacy of Deferasirox (ICL670) 20 mg/kg/Day Relative to Subcutaneous Deferoxamine in Sickle Cell Disease Patients With Iron Overload From Repeated Blood Transfusions

Conditions
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Sickle Cell Disease, Iron Overload, Hemolytic Anemia

Intervention / Treatment
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* Drug: Deferasirox (ICL670)
* Drug: Deferoxamine (DFO)


Participation Criteria
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Eligibility Criteria
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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: 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 For patients ≤ 16 years old receiving simple transfusions: lifetime history of receipt of at least 120 ml/kg of packed red blood cells, OR 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 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.

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Deferasirox (ICL670)<br>Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks. | Drug: Deferasirox (ICL670)<br>* 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.<br>|
| Experimental: Deferoxamine (DFO) then ICL670<br>Deferoxamine (DFO) subcutaneously for a weekly dose of 175 mg/kg for 24 weeks then crossed over to receive Deferasirox (ICL670) orally 20 mg/kg for a total of 104 weeks on therapy. | Drug: Deferasirox (ICL670)<br>* 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.<br>Drug: Deferoxamine (DFO)<br>* Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment | The number of participants with Adverse Events (AEs) overall and according to Medical Dictionary for Regulatory Activities (MedDRA) preferred term greater than or equal to 5% participants in any group by treatment in the first 24 weeks. | 24 Weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute Change in Serum Ferritin From Baseline to Week 24 | Absolute change from baseline serum ferritin after 24 weeks of treatment with Deferasirox (ICL670) and absolute change from baseline serum ferritin after 24 weeks of treatment with Deferoxamine. Means were adjusted for the amount of transfused blood. | Baseline, 24 Weeks | 
| Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52 | Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 24 and the absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 52 for the Deferasirox treatment group and the Deferoxamine then Deferasirox treatment group. Means were adjusted for the amount of transfused blood. | Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks | 
| Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104 | Absolute change in serum ferritin after start of treatment with Deferasirox (ICL670) to week 104 for the Deferasirox treatment group. Means were adjusted for the amount of transfused blood. | Start of Deferasirox (ICL670) treatment, 104 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell Disease, Iron Overload from Repeated Blood Transfusions, Iron Overload, Blood Transfusions