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A Protocol to Allow Treatment With ICL670 for Patients With or at Risk of Life-threatening Complications of Transfusional Iron Overload Who Are Unable to Tolerate Other Iron Chelators Because of Documented Severe Toxicity

Phase 2
Completed
Conditions
Transfusional Iron Overload
Interventions
Registration Number
NCT01044186
Lead Sponsor
Novartis Pharmaceuticals
Brief Summary

The purpose of this open-label, non-comparative, multi-center protocol was to further evaluate safety and to provide treatment with ICL670 to patients who had or were at risk of life threatening complications due to transfusional iron overload with a documented inability to tolerate any of the commercially available iron chelators due to severe toxicity rendering continued therapy either impossible or hazardous. Patients who were also ineligible for all on-going registration trials with ICL670 were included in the study. In exceptional cases, patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for the registration trials were also enrolled provided they had a well-documented, sound justification for alternative chelation therapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
30
Inclusion Criteria
  • Patients had to be at risk of life-threatening complications due to transfusional iron overload and be unable to tolerate therapy with any of the commercially available iron chelators (mainly deferoxamine and/or deferiprone) because of documented severe toxicity.
  • Patients with a degree of iron overload which was not immediately life-threatening and who were ineligible for other trials with ICL670 could also be enrolled providing they had a well-documented, sound justification for alternative chelation therapy.
  • Serum ferritin ≥ 8000 μg/L.
  • Serum ferritin < 8000μg/L and LIC of ≥ 7 mg Fe/g dry weight.
  • Patients for whom ≥ 8 blood transfusions per year were required in order to maintain the Hemoglobin level at > 9 g/dL.
  • Female patients who have reached menarche and who were sexually active had to use double barrier contraception (oral plus barrier contraception), or had to have undergone total hysterectomy and/or ovariectomy, or tubal ligation.
  • Written, voluntary informed consent.
Exclusion Criteria
  • Patients with transfusional iron overload who were not experiencing severe toxicities during therapy with other iron chelators (e.g. deferoxamine and/or deferiprone).

  • Patients with non-transfusional hemosiderosis.

  • Patients with severe liver failure as defined by a score of ≥ 10 points on the Child-Pugh scale.

  • Patients with serum creatinine 1.5 times the upper limit of normal (ULN) at screening.

  • Patients with a history of nephrotic syndrome.

  • Patients with a diagnosis of clinically relevant cataract or a previous history of clinically relevant ocular toxicity related to iron chelation therapy.

  • Patients with severe systemic diseases unrelated to iron overload and which would prevent them from undergoing treatment with ICL670.

  • Patients with psychiatric or addictive disorders which prevent them from giving informed consent or undergoing treatment with ICL670.

  • Pregnant or breast feeding patients.

  • Patients treated with systemic investigational drugs within the past four weeks or topical investigational drugs within the past seven days.

  • Any surgical or medical condition which might significantly alter the absorption or excretion of drugs as shown by evidence of any of the following:

    • History of inflammatory bowel disease
    • History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection
    • History of pancreatic injury or pancreatitis; indication of impaired pancreatic function/injury as indicated by abnormal lipase or amylase
  • Patients being considered by the investigator as potentially unreliable and/or not cooperative with regard to the protocol.

  • History of drug or alcohol abuse within the 12 months prior to dosing.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
ICL670ICL670-
Primary Outcome Measures
NameTimeMethod
To evaluate the safety profile and to provide treatment with ICL670 for patients with or at risk of life-threatening complications due to transfusional iron overload who are unable to tolerate other iron chelators because of documented severe toxicity.0 - 163 weeks
Secondary Outcome Measures
NameTimeMethod
To estimate the absolute and relative change of liver iron concentration (LIC), to be measured using appropriate methodology available at individual centers.Yearly
To evaluate the role of serum ferritin, serum iron, transferrin and transferrin saturation in monitoring iron burden in these patients.Quarterly
To evaluate the relationship between changes in LIC and serum ferritin, transferring saturation and serum iron.Yearly

Trial Locations

Locations (9)

Children's Hospital Boston

🇺🇸

Boston, Massachusetts, United States

Novartis Investigative Site

🇮🇹

Torino, Italy

Novartis investigative Site

🇬🇷

Athens, Greece

Children's Hospital of Orange County

🇺🇸

Orange, California, United States

New York Presbyterian Hospital/Weill Medical College of Cornell University

🇺🇸

New York, New York, United States

Queens Hospital Center

🇺🇸

Jamaica, New York, United States

Children's Hospital and Research Center - Oakland

🇺🇸

Oakland, California, United States

New York Methodist Hospital

🇺🇸

New York, New York, United States

Cincinnatti Children's Hospital Medical center

🇺🇸

Cincinnatti, Ohio, United States

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