Safety of ICL670 vs. Deferoxamine in Sickle Cell Disease Patients With Iron Overload Due to Blood Transfusions
Information source: Novartis
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Anemia, Sickle Cell
Intervention: ICL670 (Drug); deferoxamine (Drug)
Phase: Phase 2
Status: Completed
Sponsored by: Novartis Official(s) and/or principal investigator(s):
Novartis, Study Chair, Affiliation: Novartis
Summary
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.
Clinical Details
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
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Evaluate the safety and tolerability of multiple doses if ICL670
Secondary outcome: Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE)Evaluate the pharmacokinetics Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables Evaluate the relationship between hepatic iron and potential surrogate markers
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
Minimum age: 2 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
U. of S. Alabama Medical Center, Mobile, Alabama 36604, United States
Children's Hospital & Research Center, Oakland, California 94609, United States
Children's Hospital Los Angeles, Los Angeles, California 90027, United States
Loma Linda University Medical Center, Loma Linda, California 92354, United States
Colorado Sickle Cell Treatment and Research Center, Denver, Colorado 80262, United States
Howard University Hospital, Washington, District of Columbia 20059, United States
Tampa Children's Hospital at St Joseph's, Tampa, Florida 33607, United States
Adult Sickle Cell Clinic, Medical College of Georgia, Augusta, Georgia 30912, United States
Georgia Comprehensive Sickle cell Center, Grady Hospital, Atlanta, Georgia 30335, United States
University of Illinois at Chicago, Chicago, Illinois 60612, United States
Children's Memorial Hospital, Chicago, Illinois 60614, United States
Tulane University Sickle Cell Center, New Orleans, Louisiana 70112, United States
Children's Hospital, Department of Hematology/Oncology, New Orleans, Louisiana 70118, United States
Boston Medical Center, Boston, Massachusetts 02118, United States
Children's Hospital Boston, Division of Hematology/Oncology, Boston, Massachusetts 02115, United States
Karmanos Cancer Institute, Detroit, Michigan 48201, United States
NY Methodist Hospital, Brooklyn, New York 11215, United States
Sickle Cell Center, Montefiore Hospital, Bronx, New York 10467, United States
U. Of Rochester Medical Center, Rochester, New York 14642, United States
Weill Medical College of Cornell University, New York, New York 10021, United States
Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
Children's Hospital Medical Center, Cincinnati, Ohio 45229, United States
James Cancer Hospital, Columbus, Ohio 43210, United States
Barrett Center, University of Cincinnati, Cincinnati, Ohio 45219, United States
Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States
Penn State Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, United States
Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, United States
Santee Hematology/Oncology, Sumter, South Carolina 29150, United States
Palmetto Health Clinical Trials, Columbia, South Carolina 29203, United States
Liberty Hematology Oncology Center, Columbia, South Carolina 29203, United States
Baylor College of Medicine, Houston, Texas 77030, United States
Scott and White Memorial Hospital & Clinics, Temple, Texas 76508, United States
Texas Children's Hospital/Baylor College of Medicine, Houston, Texas 77030, United States
Children's Hospital of the King's Daughter, Norfolk, Virginia 23507, United States
Additional Information
Starting date: May 2003
Ending date: December 2003
Last updated: September 25, 2007
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