Transfusional iron overload
Conditions
Sponsors
Novartis Pharma Services AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients presenting with transfusion-related iron overload (independent of underlying condition) with transfusional iron overload as shown by a serum ferritin level of = 1000 ng/ml, or with serum ferritin 20 transfusions or 100ml/kg of packed red blood cells) and LIC > 2mg Fe/g dw (as confirmed by R2-MRI). •age = 2 years • Adult patients: written informed consent • Pediatric patients: written informed consent by their parents or legal guardians on the patient’s behalf in accordance with the national legislation. If capable, all patients should also personally sign their written informed assent. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: • non-transfusion-related hemosiderosis • clinical evidence supporting the need of intensive chelation • mean levels of alanine aminotransferase (ALT) > 300 U/l • uncontrolled systemic hypertension • serum creatinine above the upper limit of normal (ULN) • history of nephrotic syndrome • history of clinically relevant ocular toxicity related to iron chelation • systemic diseases which would prevent the patient from undergoing study treatment • psychiatric or addictive disorders which prevent them from giving their informed consent or undergoing study treatment • pregnant or breastfeeding patients • treatment with systemic investigational drugs within the past 4 weeks or topical investigational drug within the past 7 days • any other surgical or medical condition which might significantly alter the absorption, distribution, metabolism or excretion of any drug • history or likelihood of non-compliance to medical regimens • history of drug or alcohol abuse within the past 12 months or evidence of such abuse during the run-in period • positive test to HIV •life expectancy of < 1year • pediatric patients only: body weight which prevents the use of the smallest tablet strength (125 mg) for proper dosing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate if starting doses of ICL670, based on transfusion history, and subsequent dose titration can provide clinically acceptable chelation, as measured by serum ferritin, to patients presenting with transfusional hemosiderosis and pre-existing serum ferritin levels of = 1000 ng/ml or patients presenting with serum ferritin 20 transfusions or 100ml/kg of packed red blood cells) and LIC > 2mg Fe/g dw (as confirmed by R2-MRI). Clinically acceptable chelation will be assessed by comparison of serum ferritin at baseline vs 52 weeks of treatment with ICL670.;Secondary Objective: • Evaluate the safety and tolerability of ICL670 given for up to 52 weeks • Evaluate efficacy (LIC maintenance, relation between serum ferritin and LIC), tolerability and safety in the subgroup of patients with baseline LIC<7 mg Fe/g dw • Evaluate the relationship between serum ferritin and potential surrogate markers • Evaluate dose adjustment regimens as dictated by efficacy and safety parameters in comparison to transfusional burdens. • Evaluate efficacy and safety by underlying condition • Assess drug usage compliance • Evaluate the impact of iron chelation therapy on quality of life • Evaluate patient satisfaction with ICL670 • Evaluate the change in LIC via non-invasive R2-MRI and the relationship between LIC and serum ferritin. • Evaluate cardiac iron overload and cardiac function in a substudy in 85 patients aged = 10 years ;Primary end point(s): Difference in serum ferritin from baseline vs. 52 weeks of treatment. If no 52 week serum ferritin value is present then comparison will be between baseline and the last observation. | — |
Countries
Austria, Denmark, Germany, Italy, Spain, United Kingdom
Outcome results
None listed