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

Sponsor

Novartis Pharmaceuticals (Industry)

Overall Status

Completed

CT.gov ID

NCT00067080

Collaborator

(none)

195

Enrollment

Locations

Arm

5.7

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anemia, Sickle Cell	Drug: ICL670, deferoxamine	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

195 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (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

Study Start Date :

May 1, 2003

Actual Primary Completion Date :

Jul 1, 2007

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ICL670 + deferoxamine	Drug: ICL670, deferoxamine Other Names: deferasirox

Arm

Intervention/Treatment

Experimental: ICL670 + deferoxamine

Drug: ICL670, deferoxamine

Other Names:

deferasirox

Outcome Measures

Primary Outcome Measures

Evaluate the safety and tolerability of multiple doses of ICL670 [1 year]

Secondary Outcome Measures

Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE) [at baseline, after 24 weeks and at 1year (end of study)]
Evaluate the pharmacokinetics [24 hours post-dose @ 4, 12, 24 and 52 weeks]
Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables [at 24 and 52 weks pre-dose]
Evaluate the relationship between hepatic iron and potential surrogate markers [at screen, at washout, then every 2 weeks for the first 12 weeks followed by every 4 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

2 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	U. of S. Alabama Medical Center	Mobile	Alabama	United States	36604
2	Loma Linda University Medical Center	Loma Linda	California	United States	92354
3	Children's Hospital Los Angeles	Los Angeles	California	United States	90027
4	Children's Hospital & Research Center	Oakland	California	United States	94609
5	Colorado Sickle Cell Treatment and Research Center	Denver	Colorado	United States	80262
6	Howard University Hospital	Washington, D.C.	District of Columbia	United States	20059
7	Tampa Children's Hospital at St Joseph's	Tampa	Florida	United States	33607
8	Georgia Comprehensive Sickle cell Center, Grady Hospital	Atlanta	Georgia	United States	30335
9	Adult Sickle Cell Clinic, Medical College of Georgia	Augusta	Georgia	United States	30912
10	University of Illinois at Chicago	Chicago	Illinois	United States	60612
11	Children's Memorial Hospital	Chicago	Illinois	United States	60614
12	Tulane University Sickle Cell Center	New Orleans	Louisiana	United States	70112
13	Children's Hospital, Department of Hematology/Oncology	New Orleans	Louisiana	United States	70118
14	Children's Hospital Boston, Division of Hematology/Oncology	Boston	Massachusetts	United States	02115
15	Boston Medical Center	Boston	Massachusetts	United States	02118
16	Karmanos Cancer Institute	Detroit	Michigan	United States	48201
17	NY Methodist Hospital	Brooklyn	New York	United States	11215
18	Weill Medical College of Cornell University	New York	New York	United States	10021
19	U. Of Rochester Medical Center	Rochester	New York	United States	14642
20	Sickle Cell Center, Montefiore Hospital	The Bronx	New York	United States	10467
21	Wake Forest University School of Medicine	Winston-Salem	North Carolina	United States	27106
22	Barrett Center, University of Cincinnati	Cincinnati	Ohio	United States	45219
23	Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
24	James Cancer Hospital	Columbus	Ohio	United States	43210
25	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania	United States	17033
26	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
27	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15213
28	Liberty Hematology Oncology Center	Columbia	South Carolina	United States	29203
29	Palmetto Health Clinical Trials	Columbia	South Carolina	United States	29203
30	Santee Hematology/Oncology	Sumter	South Carolina	United States	29150
31	Baylor College of Medicine	Houston	Texas	United States	77030
32	Texas Children's Hospital/Baylor College of Medicine	Houston	Texas	United States	77030
33	Scott and White Memorial Hospital & Clinics	Temple	Texas	United States	76508
34	Children's Hospital of the King's Daughter	Norfolk	Virginia	United States	23507