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

Anemia, Sickle Cell Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00067080
• Other study ID #: CICL670A0109
• Status: Completed
• Phase: Phase 2
• First received: August 11, 2003
• Last updated: August 18, 2017
• Start date: May 2003

Study information

• Verified date: August 2017
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 195
• Est. primary completion date: July 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Hemosiderosis
• Iron Overload

Intervention

Drug:
• ICL670, deferoxamine

Locations

Country	Name	City	State
United States	Georgia Comprehensive Sickle cell Center, Grady Hospital	Atlanta	Georgia
United States	Adult Sickle Cell Clinic, Medical College of Georgia	Augusta	Georgia
United States	Boston Medical Center	Boston	Massachusetts
United States	Children's Hospital Boston, Division of Hematology/Oncology	Boston	Massachusetts
United States	NY Methodist Hospital	Brooklyn	New York
United States	Children's Memorial Hospital	Chicago	Illinois
United States	University of Illinois at Chicago	Chicago	Illinois
United States	Barrett Center, University of Cincinnati	Cincinnati	Ohio
United States	Children's Hospital Medical Center	Cincinnati	Ohio
United States	Liberty Hematology Oncology Center	Columbia	South Carolina
United States	Palmetto Health Clinical Trials	Columbia	South Carolina
United States	James Cancer Hospital	Columbus	Ohio
United States	Colorado Sickle Cell Treatment and Research Center	Denver	Colorado
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania
United States	Baylor College of Medicine	Houston	Texas
United States	Texas Children's Hospital/Baylor College of Medicine	Houston	Texas
United States	Loma Linda University Medical Center	Loma Linda	California
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	U. of S. Alabama Medical Center	Mobile	Alabama
United States	Children's Hospital, Department of Hematology/Oncology	New Orleans	Louisiana
United States	Tulane University Sickle Cell Center	New Orleans	Louisiana
United States	Weill Medical College of Cornell University	New York	New York
United States	Children's Hospital of the King's Daughter	Norfolk	Virginia
United States	Children's Hospital & Research Center	Oakland	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	U. Of Rochester Medical Center	Rochester	New York
United States	Santee Hematology/Oncology	Sumter	South Carolina
United States	Tampa Children's Hospital at St Joseph's	Tampa	Florida
United States	Scott and White Memorial Hospital & Clinics	Temple	Texas
United States	Sickle Cell Center, Montefiore Hospital	The Bronx	New York
United States	Howard University Hospital	Washington, D.C.	District of Columbia
United States	Wake Forest University School of Medicine	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Cel — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Evaluate the safety and tolerability of multiple doses of ICL670		1 year
Secondary	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)
Secondary	Evaluate the pharmacokinetics		24 hours post-dose @ 4, 12, 24 and 52 weeks
Secondary	Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables		at 24 and 52 weks pre-dose
Secondary	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

External Links

•   Novartis Clinical Trial Results Database
•   Results for CICL670A0109 from the Novartis Clinical Trials website
•   Results for CICL670A0109 from the Novartis Clinical Trials website