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

Condition(s) targeted: Beta-Thalassemia

Intervention: ICL670 (Drug); deferoxamine (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: Novartis

Official(s) and/or principal investigator(s):
Novartis, Study Chair, Affiliation: Novartis

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.

Official title: A Randomized, Comparative, Open Label Phase III Trial on Efficacy & Safety of Long-Term Treatment With ICL670 Compared to Deferoxamine in Beta-Thalassemia Patients With Transfusional Hemosiderosis

Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Primary outcome: Demonstrate non-inferiority to deferoxamine in its effects on liver iron content (LIC)

Secondary outcome:

Evaluate tolerability profile

Estimate absolute and relative change of LIC and Total body iron excretion

Evaluation relationship between LIC and potential surrogate markers

Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variable

Detailed 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.

Minimum age: 2 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

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.

Children's Hospital Oakland, Oakland, California 94609, United States

Stanford Hospital, Stanford, California 94305-5208, United States

Children's Hospital of Los Angeles, Los Angeles, California 90027-6062, United States

Children's Memorial Hospital, Chicago, Illinois 60614-3394, United States

Children's Hospital Boston, Boston, Massachusetts 02115, United States

Weill Medical College of Cornell University, New York, New York 10021, United States

Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104-4318, United States

Starting date: May 2003
Last updated: August 14, 2006