Efficacy and Safety Study of Deferasirox in Patients With Non-transfusion Dependent Thalassemia (THETIS)

Primary Outcome Measures:

• Change in liver iron concentration [ Time Frame: baseline, 52 weeks ]
  Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment
  
  

Secondary Outcome Measures:

• Medical Outcomes Study Short Form-36 [ Time Frame: baseline, up to 156 weeks ]
  Absolute change from baseline at 52, 104 and 156 weeks. The SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perseptions, Vitality, Social functioning, Role limitations due to emotional problems, General mental health and Health change over the past year.
  
  
• Pediatric Quality of Life Questionnaires [ Time Frame: baseline, up to 156 weeks ]
  Absolute change from baseline at 52, 104 and 156 weeks. The PedsOL is a modular approach to measuring health-related quality of life in children and adolescents (13 to 18 years). 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, up to 260 weeks ]
  Absolute change in liver iron concentration measured by MRI from baseline up to 260 weeks(approximately every 6 months)
  
  
• Correlation between serum ferritin and liver iron concentration [ Time Frame: baseline, up to 260 weeks ]
  Change in ferritin vs change in liver iron concentration from baseline up to 260 weeks
  
  
• Change in serum ferritin [ Time Frame: baseline, up to 260 weeks ]
  Absolute change in serum ferritin from baseline over time up to 260 weeks
  
  
• Endocrine function laboratory parameters [ Time Frame: baseline, up to 260 weeks ]
  Absolute change over time from baseline up to 260 weeks 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: up to 24 weeks ]
  A subset of patients (Pharmacokinetic Analysis Set) will be used in all pharmacokinetic data analysis and PK summary statistics. The PK parameters, AUCtau, Cmax 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: up to 260 weeks ]
  The incidence of treatment-emergent Adverse Events (AEs) will be summarized. Deaths (reportable as SAEs) and non-fatal SAEs will be listed. Significant changes in laboratory values, ECG parameters, vital signs, ocular and auditory examinations after start of study will be documented as AEs.
  
  
• Change in liver iron concentration [ Time Frame: every 24 weeks following baseline to week 260 ]
  Response rate in patients with baseline LIC >15 mg Fe/g dw defined as proportion of patients achieving LIC <5mg Fe/g dw and time to achieving LIC <5mg Fe/g dw.
  
  
• Change in liver iron concentration [ Time Frame: every 24 weeks from week 52 to week 260 ]
  Long term efficacy and safety of treatment to target LIC of 3mg Fe/g dw followed by one or more treatment holidays until the LIC is ≥5 mg Fe/g dw.
  
  
• Change in liver iron concentration [ Time Frame: every 24 weeks, from baseline to week 260 ]
  Absolute change from baseline LIC over time by non-transfusion dependent thalassemia (NTDT) syndrome
  
  

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. 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 in NTDT syndrome, evaluate higher doses of deferasirox, assess endocrine function and examine PK parameters.To also assess the efficacy of treatment in patients with very high LIC (>15 mg Fe/g dw) at baseline and those who need re-treatment after having reached the target LIC < 3 mg Fe/g dw during the study.