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

Phase 2
Completed
Conditions
Sickle Cell Disease
Interventions
Registration Number
NCT01090323
Lead Sponsor
Novartis Pharmaceuticals
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
185
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 & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ICL670ICL670-
Primary Outcome Measures
NameTimeMethod
Number of Participants With Adverse Events After Start of ICL6700 - 60 months

Safety as assessed by the number of participants with adverse event or death after the start of ICL670.

Secondary Outcome Measures
NameTimeMethod
Change in Serum Ferritin From Start of ICL670 to End of Study0 - 60 months

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.

Trial Locations

Locations (32)

Children's Hospital Los Angeles

🇺🇸

Los Angeles, California, United States

Children's Memorial Hospital

🇺🇸

Chicago, Illinois, United States

Medical College of Georgia

🇺🇸

Augusta, Georgia, United States

University of South Alabama College of Medicine

🇺🇸

Mobile, Alabama, United States

Tulane University Medical Center

🇺🇸

New Orleans, Louisiana, United States

Children's Hospital & Research Center at Oakland

🇺🇸

Oakland, California, United States

Howard University Hospital

🇺🇸

Washington, District of Columbia, United States

Grady Hospital, Georgia Comprehensive Sickle Cell Center

🇺🇸

Atlanta, Georgia, United States

Loma Linda University Medical Center

🇺🇸

Loma Linda, California, United States

Wake Forest University Health Sciences

🇺🇸

Winston-Salem, North Carolina, United States

St. Jude's Children Research Hospital

🇺🇸

Memphis, Tennessee, United States

Children's Hospital of the King's Daughters

🇺🇸

Norfolk, Virginia, United States

Novartis Investigative Site

🇬🇧

London, United Kingdom

The Methodist Hospital

🇺🇸

Houston, Texas, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

University of Colorado Health Science Center

🇺🇸

Denver, Colorado, United States

St Joseph Children's Hospital of Tampa

🇺🇸

Tampa, Florida, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Children's Hospital Medical Center

🇺🇸

Cincinnati, Ohio, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

Children's Hospital of Pittsburgh

🇺🇸

Pittsburgh, Pennsylvania, United States

Palmetto Health Richland

🇺🇸

Columbia, South Carolina, United States

University of Illinois at Chicago

🇺🇸

Chicago, Illinois, United States

Milton S. Hershey Medical Center

🇺🇸

Hershey, Pennsylvania, United States

Yasin

🇺🇸

Philadelphia, Pennsylvania, United States

New York Methodist Hospital

🇺🇸

Brooklyn, New York, United States

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

LSUHSC Dept of Pediatrics

🇺🇸

Shreveport, Louisiana, United States

Santee Hematology/Oncology

🇺🇸

Sumter, South Carolina, United States

Scott & White Memorial Hospital

🇺🇸

Temple, Texas, United States

New York Presbyterian Hospital

🇺🇸

New York, New York, United States

Montefiore Medical Center

🇺🇸

Bronx, New York, United States

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