Clinical trial NCT00067080: Safety of ICL670 vs. Deferoxamine in Sickle Cell Disease Patients With Iron Overload Due to Blood Transfusions
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Anemia, Sickle Cell
Keywords: Sickle cell disease
iron overload
deferoxamine
hemosiderosis
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2003-08-13
Enrollment: 195
Sex: ALL
Minimum age (years): 2
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
measure: Evaluate the safety and tolerability of multiple doses of ICL670
timeFrame: 1 year
Secondary outcomes:
measure: Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE)
timeFrame: at baseline, after 24 weeks and at 1year (end of study)
measure: Evaluate the pharmacokinetics
timeFrame: 24 hours post-dose @ 4, 12, 24 and 52 weeks
measure: Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables
timeFrame: at 24 and 52 weks pre-dose
measure: Evaluate the relationship between hepatic iron and potential surrogate markers
timeFrame: at screen, at washout, then every 2 weeks for the first 12 weeks followed by every 4 weeks
Other outcomes:
Locations:
city: Mobile
country: United States
facility: U. of S. Alabama Medical Center
state: Alabama
city: Loma Linda
country: United States
facility: Loma Linda University Medical Center
state: California
city: Los Angeles
country: United States
facility: Children's Hospital Los Angeles
state: California
city: Oakland
country: United States
facility: Children's Hospital & Research Center
state: California
city: Denver
country: United States
facility: Colorado Sickle Cell Treatment and Research Center
state: Colorado
city: Washington, D.C.
country: United States
facility: Howard University Hospital
state: District of Columbia
city: Tampa
country: United States
facility: Tampa Children's Hospital at St Joseph's
state: Florida
city: Atlanta
country: United States
facility: Georgia Comprehensive Sickle cell Center, Grady Hospital
state: Georgia
city: Augusta
country: United States
facility: Adult Sickle Cell Clinic, Medical College of Georgia
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Chicago
country: United States
facility: Children's Memorial Hospital
state: Illinois
city: New Orleans
country: United States
facility: Tulane University Sickle Cell Center
state: Louisiana
city: New Orleans
country: United States
facility: Children's Hospital, Department of Hematology/Oncology
state: Louisiana
city: Boston
country: United States
facility: Children's Hospital Boston, Division of Hematology/Oncology
state: Massachusetts
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Brooklyn
country: United States
facility: NY Methodist Hospital
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell University
state: New York
city: Rochester
country: United States
facility: U. Of Rochester Medical Center
state: New York
city: The Bronx
country: United States
facility: Sickle Cell Center, Montefiore Hospital
state: New York
city: Winston-Salem
country: United States
facility: Wake Forest University School of Medicine
state: North Carolina
city: Cincinnati
country: United States
facility: Barrett Center, University of Cincinnati
state: Ohio
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center
state: Ohio
city: Columbus
country: United States
facility: James Cancer Hospital
state: Ohio
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Columbia
country: United States
facility: Liberty Hematology Oncology Center
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Clinical Trials
state: South Carolina
city: Sumter
country: United States
facility: Santee Hematology/Oncology
state: South Carolina
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital/Baylor College of Medicine
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital & Clinics
state: Texas
city: Norfolk
country: United States
facility: Children's Hospital of the King's Daughter
state: Virginia
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: Vichinsky E, Onyekwere O, Porter J, Swerdlow P, Eckman J, Lane P, Files B, Hassell K, Kelly P, Wilson F, Bernaudin F, Forni GL, Okpala I, Ressayre-Djaffer C, Alberti D, Holland J, Marks P, Fung E, Fischer R, Mueller BU, Coates T; Deferasirox in Sickle Cell Investigators. A randomised comparison of deferasirox versus deferoxamine for the treatment of transfusional iron overload in sickle cell disease. Br J Haematol. 2007 Feb;136(3):501-8. doi: 10.1111/j.1365-2141.2006.06455.x.