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

Novartis

Status and phase

Completed

Phase 2

Conditions

Anemia, Sickle Cell

Treatments

Drug: ICL670, deferoxamine

Study type

Interventional

Funder types

Industry

Identifiers

NCT00067080

CICL670A0109

Details and patient eligibility

About

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.

Full 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.

Enrollment

195 patients

Sex

All

Ages

2+ years old

Volunteers

No Healthy Volunteers

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