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

Phase 2

Completed

• Conditions: Sickle Cell Disease; Iron Overload; Hemolytic Anemia
• Interventions: Drug: Deferasirox (ICL670); Drug: Deferoxamine (DFO)

• Registration Number: NCT00110617
• Lead Sponsor: Novartis Pharmaceuticals

Brief 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.

Detailed Description

Not available

Study Timeline

• Study Start: 2005-05
• Study First Submitted: 2005-05-10
• Study First Submitted QC: 2005-05-10
• Study First Posted: 2005-05-11
• Primary Completion: 2008-04
• Study Completion: 2008-04
• Results First Submitted: 2011-01-11
• Results First Submitted QC: 2011-03-31
• Status Verified: 2011-05
• Results First Posted: 2011-05-02
• Last Update Submitted: 2011-05-23
• Last Update Posted: 2011-05-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 212

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Deferasirox (ICL670)	Deferasirox (ICL670)	Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks.
Deferoxamine (DFO) then ICL670	Deferasirox (ICL670)	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.
Deferoxamine (DFO) then ICL670	Deferoxamine (DFO)	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.

Primary Outcome Measures

Name	Time	Method
The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment	24 Weeks	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.

Secondary Outcome Measures

Name	Time	Method
Absolute Change in Serum Ferritin From Baseline to Week 24	Baseline, 24 Weeks	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.
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 24 and to Week 52	Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks	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.
Absolute Change in Serum Ferritin After Start of Treatment With Deferasirox (ICL670) to Week 104	Start of Deferasirox (ICL670) treatment, 104 Weeks	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.

Trial Locations

Locations (58)

University of Alabama Pediatric Hematology/Oncology; 🇺🇸 Birmingham, Alabama, United States

University of Alabama Medical center; 🇺🇸 Birmingham, Alabama, United States

University of South Alabama Medical Center; 🇺🇸 Mobile, Alabama, United States

University of South Alabama; 🇺🇸 Mobile, Alabama, United States

Loma Linda University Medical Center; 🇺🇸 Loma Linda, California, United States

Children's Hospital Oakland; 🇺🇸 Oakland, California, United States

Center for Cancer and Blood Disorders; 🇺🇸 Washington, District of Columbia, United States

Children's National Medical Center; 🇺🇸 Washington, District of Columbia, United States

Howard University Hospital; 🇺🇸 Washington, District of Columbia, United States

Miami Children's Hospital; 🇺🇸 Miami, Florida, United States

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