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Safety of ICL670 vs. Deferoxamine in Sickle Cell Disease Patients With Iron Overload Due to Blood Transfusions

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00067080
First Posted: August 13, 2003
Last Update Posted: August 22, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by:
Novartis
  Purpose
The purpose of this study is to determine if the new orally active iron chelator, ICL670, is as safe as deferoxamine in preventing accumulation of iron in the body while a patient is undergoing repeated blood transfusions.

Condition Intervention Phase
Anemia, Sickle Cell Drug: ICL670, deferoxamine Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open Label, Phase II Study on Safety and Efficacy of Long Term Treatment of ICL670 Relative to Deferoxamine in Sickle Cell Disease Patients With Transfusional Hemosiderosis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Evaluate the safety and tolerability of multiple doses of ICL670 [ Time Frame: 1 year ]

Secondary Outcome Measures:
  • Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE) [ Time Frame: at baseline, after 24 weeks and at 1year (end of study) ]
  • Evaluate the pharmacokinetics [ Time Frame: 24 hours post-dose @ 4, 12, 24 and 52 weeks ]
  • Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables [ Time Frame: at 24 and 52 weks pre-dose ]
  • Evaluate the relationship between hepatic iron and potential surrogate markers [ Time Frame: at screen, at washout, then every 2 weeks for the first 12 weeks followed by every 4 weeks ]

Enrollment: 195
Study Start Date: May 2003
Primary Completion Date: July 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ICL670 + deferoxamine Drug: ICL670, deferoxamine
Other Name: deferasirox

Detailed Description:
Patients who require repeated blood transfusions accumulate iron in the body as blood cells contain iron and there is no natural body mechanism to eliminate it. After a while the iron levels get high enough to be toxic to the body. The current therapy of choice is deferoxamine which does a good job of removing excess iron, but is difficult to administer. Deferoxamine requires subcutaneous (under the skin) infusions over 4 to 8 hours nightly 3 to 7 nights per week. In addition to the need to wear an infusion pump nightly, adverse reactions around the site of the injection are frequent.
  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age greater than or equal to 2 years
  • Sickle cell disease patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
  • Serum ferritin greater than 1000 mg/ml
  • Liver iron content greater than 2 mg iron/g dw assessed by means of superconducting quantum interference device (SQUID) for patients who receive simple transfusions and greater than 5 mg iron/ g dw for patients who receive exchange transfusions or who have a history of intermittent blood transfusion.
  • Regular transfusion aimed at maintaining % Hb A above 50% or a previous history of simple transfusion being the recipient of at least 20 units of packed red blood cells.

Exclusion Criteria:

  • Chronic anemias other than sickle cell disease
  • Documented toxicity to deferoxamine
  • Elevated liver enzymes in the year preceeding enrollment
  • Active hepatitis B or hepatitis C
  • HIV seropositivity
  • Elevated serum creatinine or significant proteinuria
  • History of nephrotic syndrome
  • Uncontrolled systemic hypertension
  • Fever and other signs/symptoms of infection within 10 days prior to the start of the study
  • Presence of clinically relevant cataract or previous history of clinically relevant ocular toxicity related to iron chelation
  • Second or third degree AV block, clinically relevant Q-T interval prolongation, or patients requiring digoxin or other drugs that prolong the Q-T interval (other than beta-adrenergic receptor blocking agents).
  • Diseases (cardiovascular, renal, hepatic, etc.) that would prevent the patient from undergoing any of the treatment options
  • Psychiatric or addictive disorders that would prevent the patient from giving informed consent
  • History of drug or alcohol abuse within the 12 months prior to the study
  • Pregnant or breast feeding patients
  • Patients treated with systemic investigational drugs within 4 weeks or topical investigational drugs within 7 days before the start of the study
  • Patients who require concomitant therapy with hydroxyurea
  • Any surgical or medical condition that might significantly alter the absorption, distribution, metabolism or excretion of any drug, such as gastrointestinal disease or major surgery, renal disease, difficulty voiding or urinary obstruction, or impaired pancreatic function
  • Non-compliant or unreliable patients
  • Patients unable to undergo any study procedures such as the hearing or eye tests, or the liver echocardiography
  • Patients unable to undergo SQUID examination
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00067080


  Show 34 Study Locations
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

Additional Information:
Publications:
Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00067080     History of Changes
Other Study ID Numbers: CICL670A0109
First Submitted: August 11, 2003
First Posted: August 13, 2003
Last Update Posted: August 22, 2017
Last Verified: August 2017

Keywords provided by Novartis:
Sickle cell disease
iron overload
deferoxamine
hemosiderosis

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