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

Novartis

Status and phase

Completed

Phase 3

Conditions

Beta-Thalassemia

Treatments

Drug: deferoxamine

Drug: ICL670

Study type

Interventional

Funder types

Industry

Identifiers

NCT00061750

CICL670A0107

Details and patient eligibility

About

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.

Full 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.

Enrollment

595 patients

Sex

All

Ages

2+ years old

Volunteers

No Healthy Volunteers

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.