Back to resultsEvaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
Primary Purpose
Sickle Cell Disease
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
ICL670
Sponsored by
About this trial
This is an interventional treatment trial for Sickle Cell Disease focused on measuring Deferasirox, ICL670A, Iron chelators, Sickle Cell Disease, Transfusional Hemosiderosis
Eligibility Criteria
Inclusion Criteria:
Patients were included who met the following criteria:
- Completion of the core [Study 0109]
- Serum ferritin greater than or equal to 500 µg/L
- Ability to comply with all study-related procedures, medications, and evaluations
- Sexually active post-menarche female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
- Written informed consent and assent by the patient and or their parents or legal guardian.
Additional inclusion criteria for pediatric patients The definition of the term 'pediatric' for enrollment and study conduct was in accordance with local law. Parents or the legal guardians were fully informed by the investigator as to the requirements of the study. The pediatric patients themselves were informed according to their capabilities in a language and terms that they were able to understand. Written informed consent was obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients had to also personally sign their written informed consent.
Exclusion Criteria:
Patients who met the following criteria were to be excluded:
- History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
- Serum creatinine above the age-appropriate upper limit of normal within one week prior to entry
- Patients with ALT ≥ 500 U/L within one week prior to entry
- Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline
- Pregnancy (as indicated by serum β-HCG pregnancy test for all female patients with the potential to become pregnant) and patients who are breastfeeding
- Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit
Other protocol-defined inclusion/exclusion criteria may apply
Sites / Locations
- University of South Alabama College of Medicine
- Loma Linda University Medical Center
- Children's Hospital Los Angeles
- Children's Hospital & Research Center at Oakland
- University of Colorado Health Science Center
- Howard University Hospital
- St Joseph Children's Hospital of Tampa
- Grady Hospital, Georgia Comprehensive Sickle Cell Center
- Medical College of Georgia
- University of Illinois at Chicago
- Children's Memorial Hospital
- Tulane University Medical Center
- LSUHSC Dept of Pediatrics
- Children's Hospital Boston
- Karmanos Cancer Institute
- Montefiore Medical Center
- New York Methodist Hospital
- New York Presbyterian Hospital
- Wake Forest University Health Sciences
- Children's Hospital Medical Center
- University of Cincinnati
- Milton S. Hershey Medical Center
- Yasin
- Children's Hospital of Pittsburgh
- Palmetto Health Richland
- Santee Hematology/Oncology
- St. Jude's Children Research Hospital
- Texas Children's Hospital
- The Methodist Hospital
- Scott & White Memorial Hospital
- Children's Hospital of the King's Daughters
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
- Novartis Investigative Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
ICL670
Arm Description
Outcomes
Primary Outcome Measures
Number of Participants With Adverse Events After Start of ICL670
Safety as assessed by the number of participants with adverse event or death after the start of ICL670.
Secondary Outcome Measures
Change in Serum Ferritin From Start of ICL670 to End of Study
The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01090323
Brief Title
Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
Official Title
A One Year Open Label, Non-comparative Extension to a Randomized, Multicenter, Phase II Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration (LIC) of Repeated Doses of 5-30mg/kg/Day ICL670 Relative to Deferoxamine (DFO) in Sickle Cell Disease (SCD) Patients With Transfusional Hemosideresis (THS) [Amendment 3: Extension Prolonged to 4-years]
Study Type
Interventional
2. Study Status
Record Verification Date
May 2011
Overall Recruitment Status
Completed
Study Start Date
July 2004 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Name of the Sponsor
Novartis Pharmaceuticals
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The safety, tolerability, effects on liver iron concentration and pharmacokinetics of ICL670 is studied in sickle cell disease patients with transfusional hemosiderosis.
Detailed Description
The treatment period started once the patient completed the core study and signed informed consent. It is continued for up to 4 years. Safety parameters were assessed every 4 weeks. Eye and Ear examinations were performed on a yearly basis. To further investigate the extent of iron overload, serum ferritin, iron, and transferrin were monitored every four weeks. The Program Safety Board monitored the safety of ICL670 during the study to evaluate and categorize any serious case reported in association with ICL670.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sickle Cell Disease
Keywords
Deferasirox, ICL670A, Iron chelators, Sickle Cell Disease, Transfusional Hemosiderosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
185 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ICL670
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
ICL670
Intervention Description
Daily doses of ICL670 were taken orally 30 minutes before breakfast. The doses range from 5-40 mg/kg and were determined based on the patient's trend in serum ferritin over time during the core study (0109) and on the frequency of blood transfusions the patient received. The treatment duration was up to 4 years.
Primary Outcome Measure Information:
Title
Number of Participants With Adverse Events After Start of ICL670
Description
Safety as assessed by the number of participants with adverse event or death after the start of ICL670.
Time Frame
0 - 60 months
Secondary Outcome Measure Information:
Title
Change in Serum Ferritin From Start of ICL670 to End of Study
Description
The main efficacy variable was change in serum ferritin in response to therapy with ICL670. Due to variability of serum ferritin, end of study was considered as the mean of at most the last 3 available observations after the start of ICL670.
Time Frame
0 - 60 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients were included who met the following criteria:
Completion of the core [Study 0109]
Serum ferritin greater than or equal to 500 µg/L
Ability to comply with all study-related procedures, medications, and evaluations
Sexually active post-menarche female patients must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or oophorectomy, tubal ligation or be postmenopausal defined by amenorrhea for at least 12 months.
Written informed consent and assent by the patient and or their parents or legal guardian.
Additional inclusion criteria for pediatric patients The definition of the term 'pediatric' for enrollment and study conduct was in accordance with local law. Parents or the legal guardians were fully informed by the investigator as to the requirements of the study. The pediatric patients themselves were informed according to their capabilities in a language and terms that they were able to understand. Written informed consent was obtained from their legal guardian on the patient's behalf in accordance with national legislation. If capable, all patients had to also personally sign their written informed consent.
Exclusion Criteria:
Patients who met the following criteria were to be excluded:
History of non-compliance to medical regimens and patients who are considered potentially unreliable and/or not cooperative
Serum creatinine above the age-appropriate upper limit of normal within one week prior to entry
Patients with ALT ≥ 500 U/L within one week prior to entry
Evidence of chelation-related cataracts or hearing loss within 4 weeks prior to baseline
Pregnancy (as indicated by serum β-HCG pregnancy test for all female patients with the potential to become pregnant) and patients who are breastfeeding
Patients treated with systemic investigational drug within 4 weeks prior to or with topical investigational drug within 7 days prior to the baseline visit
Other protocol-defined inclusion/exclusion criteria may apply
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
University of South Alabama College of Medicine
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 at Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
90609
Country
United States
Facility Name
University of Colorado Health Science Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80262
Country
United States
Facility Name
Howard University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20059
Country
United States
Facility Name
St Joseph Children's Hospital of Tampa
City
Tampa
State/Province
Florida
ZIP/Postal Code
33607
Country
United States
Facility Name
Grady Hospital, Georgia Comprehensive Sickle Cell Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30303
Country
United States
Facility Name
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 Medical Center
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
LSUHSC Dept of Pediatrics
City
Shreveport
State/Province
Louisiana
ZIP/Postal Code
71130
Country
United States
Facility Name
Children's Hospital Boston
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
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
New York Methodist Hospital
City
Brooklyn
State/Province
New York
ZIP/Postal Code
11215
Country
United States
Facility Name
New York Presbyterian Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Wake Forest University Health Sciences
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
Facility Name
Children's Hospital Medical Center
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Facility Name
Milton S. Hershey Medical Center
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Facility Name
Yasin
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
Palmetto Health Richland
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
St. Jude's Children Research Hospital
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
The Methodist Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Scott & White Memorial Hospital
City
Temple
State/Province
Texas
ZIP/Postal Code
76508
Country
United States
Facility Name
Children's Hospital of the King's Daughters
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23507
Country
United States
Facility Name
Novartis Investigative Site
City
Toronto
Country
Canada
Facility Name
Novartis Investigative Site
City
Creteil
Country
France
Facility Name
Novartis Investigative Site
City
Paris
Country
France
Facility Name
Novartis Investigative Site
City
Catania
Country
Italy
Facility Name
Novartis Investigative Site
City
Genova
Country
Italy
Facility Name
Novartis Investigative Site
City
Milano
Country
Italy
Facility Name
Novartis Investigative Site
City
Roma
Country
Italy
Facility Name
Novartis Investigative Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).
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