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

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]

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

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease
• Intervention / Treatment: Drug: ICL670

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.

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Phase 2

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	0 - 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	0 - 60 months

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (ACTUAL): July 1, 2009

Study Registration Dates

• First Submitted: March 15, 2010
• First Submitted That Met QC Criteria: March 18, 2010
• First Posted (ESTIMATE): March 19, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): June 6, 2011
• Last Update Submitted That Met QC Criteria: May 3, 2011
• Last Verified: May 1, 2011

More Information

Terms related to this study

• Keywords: Deferasirox; Sickle Cell Disease; ICL670A; Iron chelators; Transfusional Hemosiderosis
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Molecular Mechanisms of Pharmacological Action; Chelating Agents; Sequestering Agents; Iron Chelating Agents; Deferasirox
• Other Study ID Numbers: CICL670A0109E1; EudraCT no. 2004-000597-31 (REGISTRY: EudraCT)