Non-transfusion Dependent Thalassemia
Conditions
Keywords
Non-transfusion dependent thalassemia, NTDT, deferasirox, ICL670, LIC, Liver Iron Concentration
Brief summary
Assessed 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. Provided further assessment of the long-term efficacy and safety of deferasirox in NTDT patients with iron overload (LIC ≥ 5 mg Fe/g liver dw and SF ≥ 300 ng/mL) for up to 260 weeks.
Interventions
DRUGdeferasirox
Deferasirox dispersible tablets at strengths of 125 mg, 250 mg, and 500 mg were administered by oral daily dosing.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
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, serum creatinine \> ULN, ALT \>5 x ULN, active hepatitis B or C, cirrhosis Pediatrics Only: A patient's weight of at least 20 kg is required to allow dosing of 5 mg/kg with one tablet of 125 mg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline | Baseline, 52 weeks | Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Achieving LIC <5 mg Fe/g dw | 5 years | Time to achieving LIC \<5 mg Fe/g dw for participants with baseline LIC\>15 mg Fe/g dw during the study |
| Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period | post-baseline, up to 260 weeks | Time from the target LIC \<3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period |
| Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Baseline, 52, 104 & 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 perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\]. |
| Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Baseline, 52, 104 & 156 Weeks | The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\]. |
| Absolute Change in LIC From Baseline Over Time | 24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks | Absolute change in serum ferritin from baseline over time up to 260 weeks |
| Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up) | Baseline, End of Study (EOS): Week 260 + 30 days follow up | Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model. |
| Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw | 5 years | The percentage of participants with baseline LIC\>15 mg Fe/g dw achieving an LIC \<5 mg Fe/g dw during the study |
| Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome | Baseline, 52 Weeks | Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1) |
| Absolute Change in Serum Ferritin From Baseline After 52 Weeks | Baseline, 52 weeks | Absolute change in serum ferritin from baseline after 52 weeks of treatment |
| PK Parameters: AUCtau | pre-dose (0 hour), and at 2, and 4 hours at Week 4 | The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume). |
| PK Parameters: Cmax | pre-dose (0 hour), and at 2, and 4 hours at Week 4 | The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume |
| PK Parameters: Tmax | pre-dose (0 hour), and at 2, and 4 hours at Week 4 | The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration. |
| Plasma Pharmacokinetics (PK) Deferasirox Concentrations | Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose | Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page. |
| Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up) | Week 24, End of Study (EOS): Week 260 + 30 days follow up | Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model. |
Countries
China, Greece, Italy, Lebanon, Thailand, Tunisia, Turkey (Türkiye), United Kingdom
Participant flow
Recruitment details
At least 117 patients were planned to be enrolled; 134 patients were enrolled.
Pre-assignment details
At least 117 patients were planned to be enrolled; 134 patients were enrolled.
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC). | 134 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 4 |
| Overall Study | Death | 3 |
| Overall Study | Lost to Follow-up | 16 |
| Overall Study | Physician Decision | 4 |
| Overall Study | Pregnancy | 10 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Subject/guardian decision | 8 |
| Overall Study | Withdrawal by Subject | 21 |
Baseline characteristics
| Characteristic | Deferasirox |
|---|---|
| Age, Continuous | 28.0 years STANDARD_DEVIATION 11.1 |
| Age, Customized 18 - < 50 years | 104 participants |
| Age, Customized < 18 years | 25 participants |
| Age, Customized 50 - < 65 years | 5 participants |
| Race/Ethnicity, Customized Asian | 85 Participants |
| Race/Ethnicity, Customized Caucasian | 48 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Sex: Female, Male Female | 58 Participants |
| Sex: Female, Male Male | 76 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 68 | 0 / 66 | 2 / 134 |
| other Total, other adverse events | 26 / 68 | 58 / 66 | 84 / 134 |
| serious Total, serious adverse events | 15 / 68 | 30 / 66 | 45 / 134 |
Outcome results
Primary
Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline
Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment
Time frame: Baseline, 52 weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline | -6.68 mg Fe/g dw | Standard Deviation 7.018 |
Secondary
Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)
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 perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\].
Time frame: Baseline, 52, 104 & 156 Weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Functioning Week 52 | -0.5 scores on a scale | Standard Deviation 5.5 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Functioning Week 104 | -0.7 scores on a scale | Standard Deviation 4.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Functioning Week 156 | 0.6 scores on a scale | Standard Deviation 6.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Physical Week 52 | 0.9 scores on a scale | Standard Deviation 9.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Physical Week 104 | -1.0 scores on a scale | Standard Deviation 10.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Physical Week 156 | 1.0 scores on a scale | Standard Deviation 10.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Bodily Pain Week 52 | -0.0 scores on a scale | Standard Deviation 11.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Vitality Week 156 | 2.1 scores on a scale | Standard Deviation 9.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Social Functioning Week 52 | 0.9 scores on a scale | Standard Deviation 9.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Social Functioning Week 104 | -1.2 scores on a scale | Standard Deviation 9.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Social Functioning Week 156 | 1.6 scores on a scale | Standard Deviation 10.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Emotional Week 52 | -0.1 scores on a scale | Standard Deviation 11.3 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Emotional Week 104 | -2.5 scores on a scale | Standard Deviation 12.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Role Emotional Week 156 | 0.7 scores on a scale | Standard Deviation 11.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Health Week 52 | 1.5 scores on a scale | Standard Deviation 11.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Health Week 104 | -0.6 scores on a scale | Standard Deviation 11.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Health Week 156 | 2.8 scores on a scale | Standard Deviation 10.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Component Week 52 | -0.8 scores on a scale | Standard Deviation 7.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Component Week 104 | -1.0 scores on a scale | Standard Deviation 7.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Bodily Pain Week 104 | -1.3 scores on a scale | Standard Deviation 10.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | General Health Week 52 | -2.3 scores on a scale | Standard Deviation 9.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Bodily Pain Week 156 | 0.9 scores on a scale | Standard Deviation 12.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | General Health Pain Week 104 | -1.9 scores on a scale | Standard Deviation 9.2 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | General Health Week 156 | -1.1 scores on a scale | Standard Deviation 8.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Vitality Week 52 | 1.1 scores on a scale | Standard Deviation 9.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Vitality Week 104 | -0.2 scores on a scale | Standard Deviation 8.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Physical Component Week 156 | -0.1 scores on a scale | Standard Deviation 7.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Component Week 104 | -1.3 scores on a scale | Standard Deviation 11.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Component Week 52 | 1.1 scores on a scale | Standard Deviation 10.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | Mental Component Week 156 | 2.2 scores on a scale | Standard Deviation 10.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | SF6D Health Utility Index Week 52 | 0.0 scores on a scale | Standard Deviation 0.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | SF6D Health Utility Index Week 104 | -0.0 scores on a scale | Standard Deviation 0.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) | SF6D Health Utility Index Week 156 | 0.0 scores on a scale | Standard Deviation 0.1 |
Secondary
Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™)
The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 \[0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)\].
Time frame: Baseline, 52, 104 & 156 Weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Teenager Wk 156 | -0.9 scores on a scale | Standard Deviation 15.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Teenager Wk 52 | 0.7 scores on a scale | Standard Deviation 17.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Teenager Wk 104 | 3.1 scores on a scale | Standard Deviation 27.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Teenager Wk 156 | 10.9 scores on a scale | Standard Deviation 25.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Teenager Wk 52 | -9.3 scores on a scale | Standard Deviation 17.5 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Teenager Wk 104 | -10.0 scores on a scale | Standard Deviation 17.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Teenager Wk 156 | -5.0 scores on a scale | Standard Deviation 20.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Teenager Wk 52 | 0.7 scores on a scale | Standard Deviation 12.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Teenager Wk 156 | 1.0 scores on a scale | Standard Deviation 21.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Teenager Wk 52 | 2.3 scores on a scale | Standard Deviation 13.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Teenager Wk 104 | 1.0 scores on a scale | Standard Deviation 19.3 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psychosocial Health - Teenager Wk 52 | -3.3 scores on a scale | Standard Deviation 13 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psychosocial Health - Teenager Wk 104 | -4.0 scores on a scale | Standard Deviation 16.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Parent Wk 104 | -3.8 scores on a scale | Standard Deviation 20.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Parent Wk 156 | 2.0 scores on a scale | Standard Deviation 20.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psychosocial Health - Parent Wk 52 | -5.5 scores on a scale | Standard Deviation 15 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psychosocial Health - Parent Wk 104 | -3.2 scores on a scale | Standard Deviation 12.3 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psychosocial Health - Parent Wk 156 | -1.8 scores on a scale | Standard Deviation 14.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Parent Wk 52 | -4.6 scores on a scale | Standard Deviation 14.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Parent Wk 104 | -1.9 scores on a scale | Standard Deviation 12 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Teenager Wk 52 | 2.3 scores on a scale | Standard Deviation 13.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Teenager Wk 104 | 1.0 scores on a scale | Standard Deviation 19.3 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Teenager Wk 104 | -3.8 scores on a scale | Standard Deviation 16.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Teenager Wk 156 | -0.9 scores on a scale | Standard Deviation 15.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Psycholosocial Health - Teenager Wk 156 | 2.0 scores on a scale | Standard Deviation 19.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Teenager Wk 52 | -1.0 scores on a scale | Standard Deviation 10.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Teenager Wk 104 | -1.9 scores on a scale | Standard Deviation 14.4 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Teenager Wk 156 | 1.2 scores on a scale | Standard Deviation 15.8 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Parent Wk 52 | -2.9 scores on a scale | Standard Deviation 19 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Parent Wk 104 | 0.0 scores on a scale | Standard Deviation 18.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Functioning - Parent Wk 156 | -0.3 scores on a scale | Standard Deviation 15.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Emotional Functioning - Parent Wk 52 | -8.7 scores on a scale | Standard Deviation 19.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Parent Wk 52 | -3.7 scores on a scale | Standard Deviation 15.5 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Parent Wk 104 | -4.6 scores on a scale | Standard Deviation 18 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Social Functioning - Parent Wk 156 | -6.0 scores on a scale | Standard Deviation 20.9 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Parent Wk 52 | -3.6 scores on a scale | Standard Deviation 20.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Parent Wk 104 | 0.0 scores on a scale | Standard Deviation 11.7 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | School Functioning - Parent Wk 156 | -0.6 scores on a scale | Standard Deviation 21.1 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Parent Wk 52 | -2.9 scores on a scale | Standard Deviation 19 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Parent Wk 104 | 0.0 scores on a scale | Standard Deviation 18.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Physical Health - Parent Wk 156 | -0.3 scores on a scale | Standard Deviation 15.6 |
| Deferasirox | Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) | Total Score - Parent Wk 156 | -1.1 scores on a scale | Standard Deviation 12.9 |
Secondary
Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome
Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)
Time frame: Baseline, 52 Weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferasirox | Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome | Beta-thalassemia intermedia | -6.11 mg Fe/g dw | Standard Deviation 6.481 |
| Deferasirox | Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome | HbE beta-thalassemia | -6.18 mg Fe/g dw | Standard Deviation 7.572 |
| Deferasirox | Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome | Alpha-thalassemia intermedia (HbH disease) | -7.97 mg Fe/g dw | Standard Deviation 7.652 |
| Deferasirox | Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome | Other, specify | -6.00 mg Fe/g dw | — |
Secondary
Absolute Change in LIC From Baseline Over Time
Absolute change in serum ferritin from baseline over time up to 260 weeks
Time frame: 24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 24 | -3.67 mg Fe/g dw | Standard Deviation 3.778 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 52 | -7.02 mg Fe/g dw | Standard Deviation 7.132 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 76 | -8.93 mg Fe/g dw | Standard Deviation 8.922 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 180 | -9.94 mg Fe/g dw | Standard Deviation 9.838 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 208 | -10.04 mg Fe/g dw | Standard Deviation 10.01 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 232 | -10.58 mg Fe/g dw | Standard Deviation 10.045 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 260 | -10.57 mg Fe/g dw | Standard Deviation 10.366 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 104 | -9.63 mg Fe/g dw | Standard Deviation 9.474 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 128 | -10.03 mg Fe/g dw | Standard Deviation 9.445 |
| Deferasirox | Absolute Change in LIC From Baseline Over Time | Week 156 | -10.20 mg Fe/g dw | Standard Deviation 9.746 |
Secondary
Absolute Change in Serum Ferritin From Baseline After 52 Weeks
Absolute change in serum ferritin from baseline after 52 weeks of treatment
Time frame: Baseline, 52 weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | Absolute Change in Serum Ferritin From Baseline After 52 Weeks | -494.64 ng/mL | Standard Deviation 760.782 |
Secondary
Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up)
Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.
Time frame: Week 24, End of Study (EOS): Week 260 + 30 days follow up
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Deferasirox | Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up) | Week 24 | 0.299 correlation coefficient |
| Deferasirox | Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up) | Change from Baseline at EOS | 0.740 correlation coefficient |
Secondary
Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw
The percentage of participants with baseline LIC\>15 mg Fe/g dw achieving an LIC \<5 mg Fe/g dw during the study
Time frame: 5 years
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Deferasirox | Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw | 51.0 percentage of participants |
Secondary
PK Parameters: AUCtau
The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).
Time frame: pre-dose (0 hour), and at 2, and 4 hours at Week 4
Population: The PK analysis set consisted of all patients from FAS who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | PK Parameters: AUCtau | 678.2 hr*umol/L | Geometric Coefficient of Variation 61.9 |
Secondary
PK Parameters: Cmax
The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume
Time frame: pre-dose (0 hour), and at 2, and 4 hours at Week 4
Population: The PK analysis set consisted of all patients from FAS who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | PK Parameters: Cmax | 53.367 umol/L | Geometric Coefficient of Variation 60.96 |
Secondary
PK Parameters: Tmax
The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.
Time frame: pre-dose (0 hour), and at 2, and 4 hours at Week 4
Population: The PK analysis set consisted of all patients from FAS who had evaluable PK data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | PK Parameters: Tmax | 2.5131 hr | Geometric Coefficient of Variation 33.9321 |
Secondary
Plasma Pharmacokinetics (PK) Deferasirox Concentrations
Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.
Time frame: Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose
Population: The PK analysis set consisted of all patients from FAS who had evaluable PK data.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Deferasirox | Plasma Pharmacokinetics (PK) Deferasirox Concentrations | 4 weeks: 0hr pre-dose | 6.513 hr*umol/L | Geometric Coefficient of Variation 75.891 |
| Deferasirox | Plasma Pharmacokinetics (PK) Deferasirox Concentrations | 4 weeks: 2hr post-dose | 48.556 hr*umol/L | Geometric Coefficient of Variation 58.006 |
| Deferasirox | Plasma Pharmacokinetics (PK) Deferasirox Concentrations | 4 weeks: 4hr post-dose | 44.652 hr*umol/L | Geometric Coefficient of Variation 69.392 |
Secondary
Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up)
Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.
Time frame: Baseline, End of Study (EOS): Week 260 + 30 days follow up
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Deferasirox | Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up) | At Baseline | 0.730 correlation coefficient |
| Deferasirox | Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up) | Change from Baseline at EOS | 0.531 correlation coefficient |
Secondary
Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period
Time from the target LIC \<3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period
Time frame: post-baseline, up to 260 weeks
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deferasirox | Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period | 27.4 days |
Secondary
Time to Achieving LIC <5 mg Fe/g dw
Time to achieving LIC \<5 mg Fe/g dw for participants with baseline LIC\>15 mg Fe/g dw during the study
Time frame: 5 years
Population: The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Deferasirox | Time to Achieving LIC <5 mg Fe/g dw | 36.3 months |