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

Beta-Thalassemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00061750
• Other study ID #: CICL670A0107
• Status: Completed
• Phase: Phase 3
• First received: June 3, 2003
• Last updated: April 18, 2012
• Start date: May 2003

Study information

• Verified date: April 2012
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 595
• Est. primary completion date: November 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Beta-Thalassemia
• Thalassemia

Intervention

Drug:
• ICL670

• deferoxamine

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Children's Memorial Hospital	Chicago	Illinois
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	Weill Medical College of Cornell University	New York	New York
United States	Children's Hospital Oakland	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Stanford Hospital	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Demonstrate non-inferiority to deferoxamine in its effects on liver iron content (LIC)
Secondary	Evaluate tolerability profile
Secondary	Estimate absolute and relative change of LIC and Total body iron excretion
Secondary	Evaluation relationship between LIC and potential surrogate markers
Secondary	Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variable