An Open Label, Multi-center, Efficacy and Safety Study of Deferasirox in Iron Overloaded Patients With Non-transfusion Dependent Thalassemia (MACS1935)

• Medical Outcomes Study Short Form-36 [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  Absolute change from baseline to 52 weeks. The SF-36 is a self-administered questionnaire for adults (> 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, Role limitations due to emotional problems, General mental health and Health change over the past year.
• Pediatric Quality of Life Questionnaires [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  The PedsOL is a modular approach to measuring health-related quality of life in pediatrics (>10 but </= 18 years of age). The approach includes both a child self-report and a parent proxy-report. The 23-item PedsQL Generic Core Scales encompass the essential core domains for pediatric health related quality of life measurement: Physical functioning, emotional functioning, social functioning and school functioning.
• Change in liver iron concentration [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
  Absolute change in liver iron concentration (MRI) from baseline after 24 weeks of treatment
• serum ferritin vs liver iron concentration [ Time Frame: baseline, week 24 and week 52 ] [ Designated as safety issue: No ]
  baseline, week 24, week 52 serum ferritin versus baseline, week 24, week 52 liver iron concentration
• change in serum ferritin [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  Absolute change in serum ferritin from baseline after 52 weeks of treatment
• endocrine laboratory parameters [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  Absolute change from baseline in Total and free testosterone (males), LH and FSH (females), TSH, total and free T4, total and free T3, fasting plasma glucose, insulin, insulin resistance and cortisol.
• pk parameters [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  PAS will be used in all pharmacokinetic data analysis and PK summary statistics. Th Pk parameters, AUCtau, Cmas and tmax may be determined using non-compartmental methods for deferasirox and its iron complex. Biofluid concentrations will be expressed in mass per volume units.
• adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  number of participants with adverse events as a measure of safety and tolerability

• Medical Outcomes Study Short Form-36 [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  Absolute change from baseline to 52 weeks. The SF-36 is a self-administered questionnaire for adults (> 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, Role limitations due to emothioal problems, General mental health and Health change over the past year.
• Pediatric Quality of Life Questionnaires [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  The PedsOL is a modular approach to measuring health-related quality of life in pediatrics (>10 but </= 18 years of age). The approach includes both a child self-report and a parent proxy-report. The 23-item PedsQL Generic Core Scales encompass the essential core domains for pediatric health related quality of life measurement: Physical functioning, emothioal functioning, social functioning and school functioning.
• Change in liver iron concentration [ Time Frame: baseline, 24 weeks ] [ Designated as safety issue: No ]
  Absolute change in liver iron concentration (MRI) from baseline after 24 weeks of treatment
• serum ferritin vs liver iron concentration [ Time Frame: baseline, week 24 and week 52 ] [ Designated as safety issue: No ]
  baseline, week 24, week 52 serum ferritin versus baseline, week 24, week 52 liver iron concentration
• change in serum ferritin [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
  Absolute change in serum ferritin from baseline after 52 weeks of treatment
• endocrine laboratory parameters [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  Absolute change from baseline in Total and free testosterone (males), LH and FSH (females), TSH, total and free T4, total and free T3, fasting plasma slucoes, insulin, insulin reisitance and cortisol.
• pk parameters [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
  PAS will be used in all pharmacikinetic data analysis and PK summary statistics. Th Pk parameters, AUCtau, Cmas and tmax may be determined using non-comparmental methos for deferasirox and its iron complex. Biofluid concentrations will be expressed in mass per volume units.
• adverse events [ Time Frame: 52 weeks ] [ Designated as safety issue: Yes ]
  number of participants with adverse events as a measure of safety and tolerability

To assess the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 52 weeks of treatment.

To assess the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 24 and 52 weeks of treatment. Also, to evaluate the impact of deferasirox on the Quality of Life for adults and pediatric patients; correlate changes in serum ferritin and LIC, evaluate efficacy changes according to genotype, evaluate higher doses of deferasirox, assess endocrine function and examine pk parameters.

Inclusion Criteria:

Non-transfusion dependent congenital or chronic anemia inclusive of beta-thalassemia intermedia, HbE beta-thalassemia or alpha-thalassemia intermedia (HbH disease)/ Liver iron concentration >/= 5 mg Fe/g dw Serum Ferritin >/= 300 ng/mL -

Exclusion Criteria:

HbS-beta Thalassemia anticipated regular transfusion program during the study Blood transfusion 6 months prior to study start significant proteinuria Creatinine clearance >/= 40 ml/min ALT >5 x ULN active hepatitis B or C cirrhosis

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