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

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.