Evaluation of the Safety, Tolerability, Pharmacokinetics (PK) and Effects on Liver Iron Concentration of ICL670 Relative to Deferoxamine(DFO).

This study has been completed.
Sponsor:
Information provided by:
Novartis
ClinicalTrials.gov Identifier:
NCT01090323
First received: March 15, 2010
Last updated: May 3, 2011
Last verified: May 2011
  Purpose

The safety, tolerability, effects on liver iron concentration and pharmacokinetics of ICL670 is studied in sickle cell disease patients with transfusional hemosiderosis.


Condition Intervention Phase
Sickle Cell Disease
Drug: ICL670
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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]

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Participants With Adverse Events After Start of ICL670 [ Time Frame: 0 - 60 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 0 - 60 months ] [ Designated as safety issue: No ]
    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.


Enrollment: 185
Study Start Date: July 2004
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ICL670 Drug: ICL670
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.

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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01090323

  Hide Study Locations
Locations
United States, Alabama
University of South Alabama College of Medicine
Mobile, Alabama, United States, 36604
United States, California
Loma Linda University Medical Center
Loma Linda, California, United States, 92354
Children's Hospital Los Angeles
Los Angeles, California, United States, 90027
Children's Hospital & Research Center at Oakland
Oakland, California, United States, 90609
United States, Colorado
University of Colorado Health Science Center
Denver, Colorado, United States, 80262
United States, District of Columbia
Howard University Hospital
Washington, District of Columbia, United States, 20059
United States, Florida
St Joseph Children's Hospital of Tampa
Tampa, Florida, United States, 33607
United States, Georgia
Grady Hospital, Georgia Comprehensive Sickle Cell Center
Atlanta, Georgia, United States, 30303
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Illinois
University of Illinois at Chicago
Chicago, Illinois, United States, 60612
Children's Memorial Hospital
Chicago, Illinois, United States, 60614
United States, Louisiana
Tulane University Medical Center
New Orleans, Louisiana, United States, 70112
LSUHSC Dept of Pediatrics
Shreveport, Louisiana, United States, 71130
United States, Massachusetts
Children's Hospital Boston
Boston, Massachusetts, United States, 02118
United States, Michigan
Karmanos Cancer Institute
Detroit, Michigan, United States, 48201
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
New York Methodist Hospital
Brooklyn, New York, United States, 11215
New York Presbyterian Hospital
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Pennsylvania
Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033
Yasin
Philadelphia, Pennsylvania, United States, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, South Carolina
Palmetto Health Richland
Columbia, South Carolina, United States, 29203
Santee Hematology/Oncology
Sumter, South Carolina, United States, 29150
United States, Tennessee
St. Jude's Children Research Hospital
Memphis, Tennessee, United States, 38105
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
The Methodist Hospital
Houston, Texas, United States, 77030
Scott & White Memorial Hospital
Temple, Texas, United States, 76508
United States, Virginia
Children's Hospital of the King's Daughters
Norfolk, Virginia, United States, 23507
Canada
Novartis Investigative Site
Toronto, Canada
France
Novartis Investigative Site
Creteil, France
Novartis Investigative Site
Paris, France
Italy
Novartis Investigative Site
Catania, Italy
Novartis Investigative Site
Genova, Italy
Novartis Investigative Site
Milano, Italy
Novartis Investigative Site
Roma, Italy
United Kingdom
Novartis Investigative Site
London, United Kingdom
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: External Affairs, Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01090323     History of Changes
Obsolete Identifiers: NCT00171197
Other Study ID Numbers: CICL670A0109E1, EudraCT no. 2004-000597-31
Study First Received: March 15, 2010
Results First Received: December 21, 2010
Last Updated: May 3, 2011
Health Authority: United States: Food and Drug Administration
Italy: Ministry of Health
Canada: Health Canada
France: Comité consultatif sur le traitement de l'information en matière de recherche dans le domaine de la santé
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Novartis:
Deferasirox
ICL670A
Iron chelators
Sickle Cell Disease
Transfusional Hemosiderosis

Additional relevant MeSH terms:
Anemia, Sickle Cell
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Deferoxamine
Deferasirox
Siderophores
Iron Chelating Agents
Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 29, 2014