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

Primary Purpose

Anemia, Sickle Cell

Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ICL670, deferoxamine
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Anemia, Sickle Cell focused on measuring Sickle cell disease, iron overload, deferoxamine, hemosiderosis

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • U. of S. Alabama Medical Center
  • Loma Linda University Medical Center
  • Children's Hospital Los Angeles
  • Children's Hospital & Research Center
  • Colorado Sickle Cell Treatment and Research Center
  • Howard University Hospital
  • Tampa Children's Hospital at St Joseph's
  • Georgia Comprehensive Sickle cell Center, Grady Hospital
  • Adult Sickle Cell Clinic, Medical College of Georgia
  • University of Illinois at Chicago
  • Children's Memorial Hospital
  • Tulane University Sickle Cell Center
  • Children's Hospital, Department of Hematology/Oncology
  • Children's Hospital Boston, Division of Hematology/Oncology
  • Boston Medical Center
  • Karmanos Cancer Institute
  • NY Methodist Hospital
  • Weill Medical College of Cornell University
  • U. Of Rochester Medical Center
  • Sickle Cell Center, Montefiore Hospital
  • Wake Forest University School of Medicine
  • Barrett Center, University of Cincinnati
  • Children's Hospital Medical Center
  • James Cancer Hospital
  • Penn State Milton S Hershey Medical Center
  • Children's Hospital of Philadelphia
  • Children's Hospital of Pittsburgh
  • Liberty Hematology Oncology Center
  • Palmetto Health Clinical Trials
  • Santee Hematology/Oncology
  • Baylor College of Medicine
  • Texas Children's Hospital/Baylor College of Medicine
  • Scott and White Memorial Hospital & Clinics
  • Children's Hospital of the King's Daughter

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

ICL670 + deferoxamine

Arm Description

Outcomes

Primary Outcome Measures

Evaluate the safety and tolerability of multiple doses of ICL670

Secondary Outcome Measures

Estimate the absolute and relative change of liver iron content (LIC) and total body iron excretion (TBIE)
Evaluate the pharmacokinetics
Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables
Evaluate the relationship between hepatic iron and potential surrogate markers

Full Information

First Posted
August 11, 2003
Last Updated
August 18, 2017
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT00067080
Brief Title
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

2. Study Status

Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
May 2003 (undefined)
Primary Completion Date
July 2007 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anemia, Sickle Cell
Keywords
Sickle cell disease, iron overload, deferoxamine, hemosiderosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
195 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ICL670 + deferoxamine
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ICL670, deferoxamine
Other Intervention Name(s)
deferasirox
Primary Outcome Measure Information:
Title
Evaluate the safety and tolerability of multiple doses of ICL670
Time Frame
1 year
Secondary Outcome Measure Information:
Title
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)
Title
Evaluate the pharmacokinetics
Time Frame
24 hours post-dose @ 4, 12, 24 and 52 weeks
Title
Evaluate the relationship between pharmacokinetics, pharmacodynamics and safety variables
Time Frame
at 24 and 52 weks pre-dose
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
U. of S. Alabama Medical Center
City
Mobile
State/Province
Alabama
ZIP/Postal Code
36604
Country
United States
Facility Name
Loma Linda University Medical Center
City
Loma Linda
State/Province
California
ZIP/Postal Code
92354
Country
United States
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Children's Hospital & Research Center
City
Oakland
State/Province
California
ZIP/Postal Code
94609
Country
United States
Facility Name
Colorado Sickle Cell Treatment and Research Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Howard University Hospital
City
Washington, D.C.
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
Tampa Children's Hospital at St Joseph's
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Georgia Comprehensive Sickle cell Center, Grady Hospital
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30335
Country
United States
Facility Name
Adult Sickle Cell Clinic, Medical College of Georgia
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
University of Illinois at Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Children's Memorial Hospital
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60614
Country
United States
Facility Name
Tulane University Sickle Cell Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Children's Hospital, Department of Hematology/Oncology
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70118
Country
United States
Facility Name
Children's Hospital Boston, Division of Hematology/Oncology
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Karmanos Cancer Institute
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
NY Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
U. Of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Sickle Cell Center, Montefiore Hospital
City
The Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Wake Forest University School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27106
Country
United States
Facility Name
Barrett Center, University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
James Cancer Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Penn State Milton S Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Liberty Hematology Oncology Center
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Palmetto Health Clinical Trials
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Santee Hematology/Oncology
City
Sumter
State/Province
South Carolina
ZIP/Postal Code
29150
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Children's Hospital/Baylor College of Medicine
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Scott and White Memorial Hospital & Clinics
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Children's Hospital of the King's Daughter
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17233848
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.
Results Reference
result
Links:
URL
https://www.ncbi.nlm.nih.gov/pubmed/17233848
Description
Results for CICL670A0109 from the Novartis Clinical Trials website

Learn more about this trial

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

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