Safety of ICL670 vs. Deferoxamine in Sickle Cell Disease Patients With Iron Overload Due to Blood Transfusions
- Registration Number
- NCT00067080
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 195
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ICL670 + deferoxamine ICL670, deferoxamine -
- Primary Outcome Measures
Name Time Method Evaluate the safety and tolerability of multiple doses of ICL670 1 year
- Secondary Outcome Measures
Name Time Method Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE) at baseline, after 24 weeks and at 1year (end of study) Evaluate the pharmacokinetics 24 hours post-dose @ 4, 12, 24 and 52 weeks Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables at 24 and 52 weks pre-dose Evaluate the relationship between hepatic iron and potential surrogate markers at screen, at washout, then every 2 weeks for the first 12 weeks followed by every 4 weeks
Trial Locations
- Locations (34)
U. of S. Alabama Medical Center
🇺🇸Mobile, Alabama, United States
Loma Linda University Medical Center
🇺🇸Loma Linda, California, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital & Research Center
🇺🇸Oakland, California, United States
Colorado Sickle Cell Treatment and Research Center
🇺🇸Denver, Colorado, United States
Howard University Hospital
🇺🇸Washington, D.C., District of Columbia, United States
Tampa Children's Hospital at St Joseph's
🇺🇸Tampa, Florida, United States
Georgia Comprehensive Sickle cell Center, Grady Hospital
🇺🇸Atlanta, Georgia, United States
Adult Sickle Cell Clinic, Medical College of Georgia
🇺🇸Augusta, Georgia, United States
University of Illinois at Chicago
🇺🇸Chicago, Illinois, United States
Scroll for more (24 remaining)U. of S. Alabama Medical Center🇺🇸Mobile, Alabama, United States