The purpose of this trial is to examine the long-term safety and efficacy of ICL670 in patients with sickle cell disease and iron overload from repeated blood transfusions.

Condition	Treatment or Intervention	Phase
Sickle Cell Disease Iron Overload Hemolytic Anemia	Drug: ICL670	Phase II

Further Study Details: 

Primary Outcomes: To assess the safety of ICL670 compared to deferoxamine during 24 weeks in patients with sickle cell disease and iron overload from repeated blood transfusion.
Secondary Outcomes: Long-term safety of ICL670
Expected Total Enrollment:  210

The primary objective of this trial is to demonstrate the safety of ICL670 in patients with sickle cell disease and iron overload from repeated blood transfusion. Secondary objectives include: demonstration of the safety of ICL670 in patients receiving concomitant hydroxyurea, exploration of the hypothesis that the efficacy of ICL670 is non-inferior to deferoxamine in this population, exploration of the hypothesis that compliance with oral ICL670 is superior to compliance with subcutaneous deferoxamine and exploration of magnetic resonance imaging for assessment of efficacy of iron chelators in a sub-set of patients.

Ages Eligible for Study:  2 Years and above,  Genders Eligible for Study:  Both

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
• 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
• 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 MI, CHF 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

Please refer to this study by ClinicalTrials.gov identifier  NCT00110617

Florida
      Tampa Children's Hospital at St. Joseph's, Tampa,  Florida,  33607-6387,  United States; Recruiting
Illinois
      Children's Memorial Hospital, Chicago,  Illinois,  60614-3394,  United States; Recruiting
Pennsylvania
      Children’s Hospital of Pittsburgh, Pittsburgh,  Pennsylvania,  15213,  United States; Recruiting
      Pennsylvania Oncology/Hematology, Philadelphia,  Pennsylvania,  19106,  United States; Recruiting

Study ID Numbers:  CICL670A2201
Record last reviewed:  May 2005
Last Updated:  May 10, 2005
Record first received:  May 10, 2005
ClinicalTrials.gov Identifier:  NCT00110617
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2005-05-17