Safety & Efficacy of ICL670 vs. Deferoxamine in Beta-thalassemia Patients With Iron Overload Due to Blood Transfusions

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT00061750
First received: June 3, 2003
Last updated: April 18, 2012
Last verified: April 2012
  Purpose

The purpose of this study is to deterimine if the new orally active iron chelator, ICL670, is as effective and as safe as deferoxamine in preventing accumulation of iron in the body while a patient is undergoing repeated blood transfusions.


Condition Intervention Phase
Beta-Thalassemia
Drug: ICL670
Drug: deferoxamine
Phase 3

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, Comparative, Open Label Phase III Trial on Efficacy & Safety of Long-term Treatment With ICL670 Compared to Deferoxamine in Beta-thalassemia Patients With Transfusional Hemosiderosis

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Demonstrate non-inferiority to deferoxamine in its effects on liver iron content (LIC)

Secondary Outcome Measures:
  • Evaluate tolerability profile
  • Estimate absolute and relative change of LIC and Total body iron excretion
  • Evaluation relationship between LIC and potential surrogate markers
  • Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variable

Enrollment: 595
Study Start Date: May 2003
Primary Completion Date: November 2004 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ICL670 Drug: ICL670
Other Name: Deferasirox
Active Comparator: Deferoxamine Drug: deferoxamine

Detailed Description:

Patients who require repeated blood transfusions to live 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

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

Inclusion Criteria:

  • Beta-thalassemia patients already treated with or suitable for treatment with deferoxamine 20 to 40 mg/kg/day
  • Liver iron content greater than 2 mg iron/g dw as measured by liver biopsy
  • Need for regular transfusions 8 or more times per year

Exclusion Criteria:

  • Non-transfusional iron overload or transfusion-dependent anemias other than beta-thalassemia.
  • 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 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
  • Diseases (cardiovascular, renal, hepatic, etc.)that would prevent the patient from undergoing any of the treatment options
  • Psychiatric or additive 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
  • 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.
  • Inability to undergo a liver biopsy.
  • Patients that would need a dose of ICL670 less than 125 mg per day.
  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: NCT00061750

Locations
United States, California
Children's Hospital of Los Angeles
Los Angeles, California, United States, 90027-6062
Children's Hospital Oakland
Oakland, California, United States, 94609
Stanford Hospital
Stanford, California, United States, 94305-5208
United States, Illinois
Children's Memorial Hospital
Chicago, Illinois, United States, 60614-3394
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02115
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
United States, Pennsylvania
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, United States, 19104-4318
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided by Novartis

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00061750     History of Changes
Other Study ID Numbers: CICL670A0107
Study First Received: June 3, 2003
Last Updated: April 18, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Novartis:
Thalassemia, iron overload, deferoxamine, hemosiderosis

Additional relevant MeSH terms:
Beta-Thalassemia
Thalassemia
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Deferasirox
Deferoxamine
Chelating Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents
Siderophores

ClinicalTrials.gov processed this record on October 23, 2014