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

Novartis

Status and phase: Completed; Phase 2

Conditions: Iron Overload; Sickle Cell Disease; Hemolytic Anemia

Treatments: Drug: Deferoxamine (DFO); Drug: Deferasirox (ICL670)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00110617

CICL670A2201

Details and patient eligibility

About

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.

Enrollment: 212 patients

Sex: All

Ages: 2+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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212 participants in 2 patient groups

Deferasirox (ICL670)

Experimental group

Description:

Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks.

Treatment:

Drug: Deferasirox (ICL670)

Deferoxamine (DFO) then ICL670

Experimental group

Description:

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.

Treatment:

Drug: Deferoxamine (DFO)

Drug: Deferasirox (ICL670)