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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Anemia, Sickle Cell

Intervention / Treatment
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* Drug: ICL670, deferoxamine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 2 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ICL670 + deferoxamine<br> | Drug: ICL670, deferoxamine<br> <br> * Other names: deferasirox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety and tolerability of multiple doses of ICL670 |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, iron overload, deferoxamine, hemosiderosis