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

Sponsor:	Novartis Pharmaceuticals
Information provided by:	Novartis
ClinicalTrials.gov Identifier:	NCT00067080

Purpose

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.

Condition	Intervention	Phase
Anemia, Sickle Cell	Drug: ICL670, deferoxamine	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	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

Resource links provided by NLM:

Genetics Home Reference related topics: sickle cell disease

MedlinePlus related topics: Anemia Blood Transfusion and Donation Iron Sickle Cell Anemia

Drug Information available for: Deferoxamine Deferasirox Deferoxamine mesylate

U.S. FDA Resources

Further study details as provided by Novartis:

Primary Outcome Measures:

Evaluate the safety and tolerability of multiple doses of ICL670 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE) [ Time Frame: at baseline, after 24 weeks and at 1year (end of study) ] [ Designated as safety issue: No ]
Evaluate the pharmacokinetics [ Time Frame: 24 hours post-dose @ 4, 12, 24 and 52 weeks ] [ Designated as safety issue: No ]
Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables [ Time Frame: at 24 and 52 weks pre-dose ] [ Designated as safety issue: No ]
Evaluate the relationship between hepatic iron and potential surrogate markers [ Time Frame: at screen, at washout, then every 2 weeks for the first 12 weeks followed by every 4 weeks ] [ Designated as safety issue: No ]

Enrollment:	195
Study Start Date:	May 2003
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: ICL670 + deferoxamine	Drug: ICL670, deferoxamine Other Name: deferasirox

Detailed 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.

Eligibility

Ages Eligible for Study:	2 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00067080

Show 34 Study Locations

Sponsors and Collaborators

Novartis Pharmaceuticals

Investigators

Study Director:

Novartis Pharmaceuticals

More Information

No publications provided

Responsible Party:	External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:	NCT00067080 History of Changes
Other Study ID Numbers:	CICL670A0109
Study First Received:	August 11, 2003
Last Updated:	February 25, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Novartis:

Sickle cell disease
iron overload
deferoxamine
hemosiderosis

Additional relevant MeSH terms:

Anemia
Anemia, Sickle Cell
Hemosiderosis
Iron Overload
Hematologic Diseases
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Hemoglobinopathies
Genetic Diseases, Inborn

Iron Metabolism Disorders
Metabolic Diseases
Deferoxamine
Deferasirox
Siderophores
Iron Chelating Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 12, 2012