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

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT00110617
First received: May 10, 2005
Last updated: May 23, 2011
Last verified: May 2011
  Purpose

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.


Condition Intervention Phase
Sickle Cell Disease
Iron Overload
Hemolytic Anemia
Drug: Deferasirox (ICL670)
Drug: Deferoxamine (DFO)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Number of Participants With Adverse Events (AEs) in the First 24 Weeks of Treatment [ Time Frame: 24 Weeks ] [ Designated as safety issue: Yes ]
    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:
  • Absolute Change in Serum Ferritin From Baseline to Week 24 [ Time Frame: Baseline, 24 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Start of Deferasirox (ICL670) treatment, 24 Weeks, 52 Weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: Start of Deferasirox (ICL670) treatment, 104 Weeks ] [ Designated as safety issue: No ]
    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.


Enrollment: 212
Study Start Date: May 2005
Study Completion Date: April 2008
Primary Completion Date: April 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Deferasirox (ICL670)
Deferasirox (ICL670) 20 mg/kg orally once daily for 104 weeks.
Drug: Deferasirox (ICL670)
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.
Experimental: Deferoxamine (DFO) then 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.
Drug: Deferasirox (ICL670)
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.
Drug: Deferoxamine (DFO)
Deferoxamine was supplied in vials of 500 mg and 2000 mg administered subcutaneously for a weekly dose of 175 mg/kg.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00110617

  Show 59 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00110617     History of Changes
Other Study ID Numbers: CICL670A2201
Study First Received: May 10, 2005
Results First Received: January 11, 2011
Last Updated: May 23, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Sickle Cell Disease
Iron Overload from Repeated Blood Transfusions
Iron Overload
Blood Transfusions

Additional relevant MeSH terms:
Anemia
Anemia, Hemolytic
Anemia, Sickle Cell
Iron Overload
Hemolysis
Hematologic Diseases
Anemia, Hemolytic, Congenital
Hemoglobinopathies
Genetic Diseases, Inborn
Iron Metabolism Disorders
Metabolic Diseases
Pathologic Processes
Deferoxamine
Deferasirox
Siderophores
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on August 18, 2014