Non-transfusion Dependent Thalassemia
Conditions
Keywords
Thalassemia, thalassemia intermedia, alpha-thalassemia, beta-thalassemia, deferasirox, iron overload, non-transfusion dependent
Brief summary
CICL670A2209: This study will evaluate the safety and efficacy of deferasirox in non-transfusion dependent thalassemia patients with iron overload. Patients will be treated either with active treatment (deferasirox) or placebo for 12 months (core study phase). Patients who complete the core study phase will be offered to continue their study with the active treatment (deferasirox) in a 12 months extension phase. During the core and extension, the effects of treatment on iron overload in the liver will be evaluated using magnetic resonance imaging (MRI) assessments. CICL670A2209E1: A one-year open-label extension to a randomized, double-blind, placebo-controlled, phase II study to evaluate efficacy and safety of deferasirox in non-transfusion dependent thalassemia patients with iron overload (Thalassa).
Interventions
DRUGdeferasirox
Supplied as 125 mg, 250 mg and 500 mg tablets.
DRUGplacebo
Supplied as matching 125 mg, 250 mg and 500 mg tablets.
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
10 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Core Inclusion Criteria: * Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old * Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start * Serum ferritin \>300 ng/mL at screening Core
Exclusion criteria
* Hemoglobin S (HbS)-variants of thalassemia syndromes * Anticipated regular transfusion program during the study. Patients having a sporadic transfusion (e.g. in case of infection) throughout the study course will not be excluded * Any blood transfusion 6 months prior to study start * Creatinine clearance ≤ 60 mL/min at screening * Serum creatinine above the upper limit of normal at both screening visits * Significant proteinuria as indicated by a urine protein/urine creatinine ratio \> 1.0 mg/mg * Alanine aminotransferase (ALT) of \> 5 x the upper limit of normal at both screening visits * Concomitant therapy with hydroxyurea, erythropoietin, butyrate * History of deferasirox treatment * Pediatric patients: a patient's weight of below 20 kg Extension Inclusion Criteria: * Patients who completed the core CICL670A2209 clinical trial * Written informed consent obtained prior entry to one year extension study CICL670A2209 Extension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52 | Baseline, Week 52 | LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate. |
| Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study | Core Baseline to End of Extension Study (up to 24 months) | Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Core Study: Change in Serum Ferritin Between Baseline and Second Quarter | Baseline, (Day 106 to Day 195) | Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Second quarter serum ferritin average was the average of all serum ferritin values obtained within days 106-195. Change from baseline: second quarter serum ferritin average - baseline serum ferritin average. |
| Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | 52 Weeks | Percentage of Participants with Mild, Moderate and Severe adverse events (AE) any primary system organ class regardless of study drug relationship. A patient with multiple occurrences of an AE is counted only once in the AE category for that treatment. A patient with multiple severity ratings for an AE while on a treatment is only counted once under the maximum rating. |
| Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Baseline, Week 24, Week 52 | LIC was measured by magnetic resonance imaging technique at baseline, Week 24 and Week 52. Dose Doubling (Dose Increases) began at Week 24. |
| Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration) | Baseline, 52 weeks | The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for the following cases: * Baseline serum ferritin versus baseline LIC * Serum ferritin difference from baseline at fourth quarter versus difference from baseline in LIC at Week 52. A value of 1.0 indicates a perfect correlation. |
| Core Study: Change From Baseline in Hemoglobin at Month 12 | Baseline, Month 12 | Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin. |
| Core Study: Change From Baseline in Transferrin Saturation at Month 12 | Baseline, Month 12 | Blood was collected for transferrin saturation at Baseline and Month 12. Change from baseline= Month 12 transferrin saturation - baseline transferrin saturation. |
| Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52 | Baseline, Week 52 | LIC was measured by magnetic resonance imaging technique at baseline and Week 52. The change in liver iron concentration for participants in the placebo arm was used to assess the iron accumulation rate. |
| Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | 52 Weeks | The percentage of participants with notable laboratory results: Platelet count: (\<100 x 10\^9/L) Absolute neutrophils: (\<1.5 x 10\^9/L) Alanine aminotransferase (ALT): (\>5 x Upper limit normal (ULN) and \>2 x baseline). Aspartate aminotransferase (AST): (\>5 x ULN and \>2 x baseline) Serum creatinine: (\>33% increase from baseline and \>ULN at ≥2 consecutive post-baseline values) Creatinine clearance: (\<60 mL/min at ≥2 consecutive post-baseline values) Urinary protein/creatinine ratio: (≥ 1.0 mg/mg at ≥2 consecutive post-baseline values) |
| Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24 | Baseline, Week 24 | LIC was measured by magnetic resonance imaging technique at baseline and Week 24. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 24 with treatment as factor and baseline LIC as covariate. |
| Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | Baseline, 52 Weeks | Diastolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Diastolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥105 with an increase from baseline ≥15 mmHg Low: ≤50 with a decrease from baseline ≥15 mmHg |
| Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | Baseline, 52 Weeks | Pulse Rate was measured at each visit. A Notably Abnormal Pulse Rate was defined as a measurement in one of the following two categories: High: ≥120 with an increase from baseline ≥15 beats per minute (bpm) Low: ≤50 with a decrease from baseline ≥15 bpm |
| Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter | Core Baseline, Eighth Quarter (last 3 months of the study) | Blood was collected for serum ferritin at Core Baseline and monthly during the Eighth quarter of the Extension Study. Absolute change from Baseline: quarterly average - baseline average. A negative change from baseline indicated improvement. |
| Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | Core Baseline, Month 24 | LIC was measured by magnetic resonance imaging technique at Baseline and Month 24. A negative change from baseline indicated improvement. |
| Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration) | Core Baseline, Month 24 | The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for serum ferritin difference from Baseline at Month 24 versus LIC difference from Baseline at Month 24. A value of 1.0 indicates a perfect correlation. |
| Extension Study: Change From Baseline in Hemoglobin at Month 24 | Core Baseline, Month 24 | Blood was collected for Hemoglobin at Baseline and Month 24. Change from Baseline= Month 24 hemoglobin - Baseline hemoglobin. |
| Extension Study: Change From Baseline in Transferrin Saturation at Month 24 | Core Baseline, Month 24 | Blood was collected for transferrin saturation at Baseline and Month 24. Change from baseline= Month 24 transferrin saturation - baseline transferrin saturation. |
| Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | Baseline, 52 Weeks | Systolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Systolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥180 with an increase from baseline ≥20 mmHg Low: ≤90 with a decrease from baseline ≥20 mmHg |
| Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter | Baseline, (Day 286 to End of Study [Day 365]) | Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Fourth quarter serum ferritin average was the average of all serum ferritin values obtained within days 286- End of Study. Change from baseline: fourth quarter serum ferritin average - baseline serum ferritin average. |
Countries
Greece, Italy, Lebanon, Malaysia, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Participant flow
Pre-assignment details
There was a 4 week screening period to determine eligibility prior to randomization.
Participants by arm
| Arm | Count |
|---|---|
| 5 mg/kg/Day Deferasirox Participants received a starting dose of 5 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. | 55 |
| 10 mg/kg/Day Deferasirox Participants received a starting dose of 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks. | 55 |
| Placebo Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day for 52 weeks. Participants received a starting dose of 5 or 10 mg/kg/day deferasirox tablets orally each day in the morning for 52 weeks. After 24 weeks of treatment Liver Iron Concentration (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation. | 56 |
| Total | 166 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Core Study | Abnormal laboratory value | 0 | 0 | 1 |
| Core Study | Adverse Event | 2 | 3 | 1 |
| Core Study | Lost to Follow-up | 3 | 1 | 0 |
| Core Study | Protocol deviation | 1 | 0 | 1 |
| Core Study | Withdrawal by Subject | 1 | 2 | 2 |
| Extension Study | Administrative reasons | 0 | 0 | 1 |
| Extension Study | Adverse Event | 1 | 0 | 1 |
Baseline characteristics
| Characteristic | 5 mg/kg/Day Deferasirox | 10 mg/kg/Day Deferasirox | Placebo | Total |
|---|---|---|---|---|
| Age, Customized <18 years | 6 Participants | 7 Participants | 8 Participants | 21 Participants |
| Age, Customized >=65 years | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Age, Customized Between 18 and 65 years | 49 Participants | 47 Participants | 48 Participants | 144 Participants |
| Sex: Female, Male Female | 26 Participants | 26 Participants | 25 Participants | 77 Participants |
| Sex: Female, Male Male | 29 Participants | 29 Participants | 31 Participants | 89 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 37 / 55 | 45 / 55 | 48 / 56 |
| serious Total, serious adverse events | 11 / 55 | 12 / 55 | 16 / 56 |
Outcome results
Primary
Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.
Time frame: Baseline, Week 52
Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52 | -1.95 mg iron (Fe)/g dry weight (dw) | Standard Error 0.5 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52 | -3.80 mg iron (Fe)/g dry weight (dw) | Standard Error 0.484 |
| Placebo | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52 | 0.38 mg iron (Fe)/g dry weight (dw) | Standard Error 0.486 |
Primary
Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study
Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported.
Time frame: Core Baseline to End of Extension Study (up to 24 months)
Population: Full Analysis consisted of all randomized participants. Patients with post-baseline LIC satisfying criterion at any time during the study are counted as responder. Patients with no baseline LIC or without any post-baseline LIC measurements will be assumed as non-responder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study | 39.1 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study | 37.5 Percentage of participants |
Secondary
Core Study: Change From Baseline in Hemoglobin at Month 12
Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin.
Time frame: Baseline, Month 12
Population: Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change From Baseline in Hemoglobin at Month 12 | -1.8 g/L | Standard Deviation 5.45 |
| 10 mg/kg/Day Deferasirox | Core Study: Change From Baseline in Hemoglobin at Month 12 | -0.7 g/L | Standard Deviation 6.27 |
| Placebo | Core Study: Change From Baseline in Hemoglobin at Month 12 | -2.8 g/L | Standard Deviation 7.31 |
Secondary
Core Study: Change From Baseline in Transferrin Saturation at Month 12
Blood was collected for transferrin saturation at Baseline and Month 12. Change from baseline= Month 12 transferrin saturation - baseline transferrin saturation.
Time frame: Baseline, Month 12
Population: Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change From Baseline in Transferrin Saturation at Month 12 | -3.79 Percent saturation | Standard Deviation 14.234 |
| 10 mg/kg/Day Deferasirox | Core Study: Change From Baseline in Transferrin Saturation at Month 12 | -3.64 Percent saturation | Standard Deviation 22.443 |
| Placebo | Core Study: Change From Baseline in Transferrin Saturation at Month 12 | 3.37 Percent saturation | Standard Deviation 10.083 |
Secondary
Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24
LIC was measured by magnetic resonance imaging technique at baseline, Week 24 and Week 52. Dose Doubling (Dose Increases) began at Week 24.
Time frame: Baseline, Week 24, Week 52
Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 24 and Week 52. Only patients with dose increases after week 24, with both baseline and at least one post-baseline value were included for this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 24 (n=26,24,30) | 0.56 mg iron (Fe)/g dry weight (dw) | Standard Deviation 2.992 |
| 5 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 52 | -1.82 mg iron (Fe)/g dry weight (dw) | Standard Deviation 3.101 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 52 | -4.02 mg iron (Fe)/g dry weight (dw) | Standard Deviation 4.849 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 24 (n=26,24,30) | 0.69 mg iron (Fe)/g dry weight (dw) | Standard Deviation 3.131 |
| Placebo | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 52 | 0.62 mg iron (Fe)/g dry weight (dw) | Standard Deviation 4.128 |
| Placebo | Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 | Change from baseline at Week 24 (n=26,24,30) | 0.94 mg iron (Fe)/g dry weight (dw) | Standard Deviation 2.693 |
Secondary
Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24
LIC was measured by magnetic resonance imaging technique at baseline and Week 24. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 24 with treatment as factor and baseline LIC as covariate.
Time frame: Baseline, Week 24
Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 24. Only patients with both baseline and at least one post-baseline value were included for this analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24 | -0.87 mg iron (Fe)/g dry weight (dw) | Standard Error 0.448 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24 | -0.90 mg iron (Fe)/g dry weight (dw) | Standard Error 0.45 |
| Placebo | Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24 | -0.24 mg iron (Fe)/g dry weight (dw) | Standard Error 0.439 |
Secondary
Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52
LIC was measured by magnetic resonance imaging technique at baseline and Week 52. The change in liver iron concentration for participants in the placebo arm was used to assess the iron accumulation rate.
Time frame: Baseline, Week 52
Population: Safety Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52 | 0.26 mg iron (Fe)/g dry weight (dw) | Standard Deviation 3.501 |
Secondary
Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter
Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Fourth quarter serum ferritin average was the average of all serum ferritin values obtained within days 286- End of Study. Change from baseline: fourth quarter serum ferritin average - baseline serum ferritin average.
Time frame: Baseline, (Day 286 to End of Study [Day 365])
Population: Full Analysis set (all randomized patients). Only participants with both baseline and post-baseline values are included in analyses. If serum ferritin was missing during the fourth quarter, the last available average of serum ferritin per quarter was used for the calculation of the change from baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter | -130.47 μg/L | Standard Deviation 260.555 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter | -249.16 μg/L | Standard Deviation 389.356 |
| Placebo | Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter | 128.63 μg/L | Standard Deviation 249.689 |
Secondary
Core Study: Change in Serum Ferritin Between Baseline and Second Quarter
Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug. Second quarter serum ferritin average was the average of all serum ferritin values obtained within days 106-195. Change from baseline: second quarter serum ferritin average - baseline serum ferritin average.
Time frame: Baseline, (Day 106 to Day 195)
Population: Full Analysis set (all randomized patients). Only participants with both baseline and post-baseline values are included in analyses. If serum ferritin was missing during the second quarter, the last available average of serum ferritin per quarter was used for the calculation of the change from baseline.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Change in Serum Ferritin Between Baseline and Second Quarter | 8.20 μg/L | Standard Deviation 244.443 |
| 10 mg/kg/Day Deferasirox | Core Study: Change in Serum Ferritin Between Baseline and Second Quarter | -17.75 μg/L | Standard Deviation 368.812 |
| Placebo | Core Study: Change in Serum Ferritin Between Baseline and Second Quarter | 106.45 μg/L | Standard Deviation 330.217 |
Secondary
Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for the following cases: * Baseline serum ferritin versus baseline LIC * Serum ferritin difference from baseline at fourth quarter versus difference from baseline in LIC at Week 52. A value of 1.0 indicates a perfect correlation.
Time frame: Baseline, 52 weeks
Population: Participants from the Full Analysis Set (all randomized participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration) | Baseline | 0.653 Correlation coefficient |
| 5 mg/kg/Day Deferasirox | Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration) | Week 52 (n=134) | 0.609 Correlation coefficient |
Secondary
Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
Percentage of Participants with Mild, Moderate and Severe adverse events (AE) any primary system organ class regardless of study drug relationship. A patient with multiple occurrences of an AE is counted only once in the AE category for that treatment. A patient with multiple severity ratings for an AE while on a treatment is only counted once under the maximum rating.
Time frame: 52 Weeks
Population: Safety Analysis Set included all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Severe | 12.7 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Moderate | 27.3 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Mild | 36.4 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Severe | 18.2 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Mild | 43.6 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Moderate | 16.4 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Moderate | 21.4 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Mild | 42.9 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe | Severe | 16.1 Percentage of participants |
Secondary
Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
The percentage of participants with notable laboratory results: Platelet count: (\<100 x 10\^9/L) Absolute neutrophils: (\<1.5 x 10\^9/L) Alanine aminotransferase (ALT): (\>5 x Upper limit normal (ULN) and \>2 x baseline). Aspartate aminotransferase (AST): (\>5 x ULN and \>2 x baseline) Serum creatinine: (\>33% increase from baseline and \>ULN at ≥2 consecutive post-baseline values) Creatinine clearance: (\<60 mL/min at ≥2 consecutive post-baseline values) Urinary protein/creatinine ratio: (≥ 1.0 mg/mg at ≥2 consecutive post-baseline values)
Time frame: 52 Weeks
Population: Safety Set included all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | AST | 0 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | ALT | 0 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Urinary protein/creatinine ratio | 1.8 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Platelet count | 5.5 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Creatinine clearance | 1.8 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Absolute neutrophils | 5.5 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Serum creatinine | 0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Creatinine clearance | 1.8 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Absolute neutrophils | 3.6 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Urinary protein/creatinine ratio | 0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Serum creatinine | 5.5 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | ALT | 0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | AST | 1.8 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Platelet count | 5.5 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Urinary protein/creatinine ratio | 0 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Platelet count | 10.7 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Absolute neutrophils | 5.4 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | ALT | 1.8 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | AST | 1.8 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Serum creatinine | 0 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results | Creatinine clearance | 0 Percentage of participants |
Secondary
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure
Diastolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Diastolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥105 with an increase from baseline ≥15 mmHg Low: ≤50 with a decrease from baseline ≥15 mmHg
Time frame: Baseline, 52 Weeks
Population: Safety Set includes all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | High | 0.0 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | Low | 14.5 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | High | 0.0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | Low | 10.9 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | High | 0.0 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure | Low | 14.3 Percentage of participants |
Secondary
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate
Pulse Rate was measured at each visit. A Notably Abnormal Pulse Rate was defined as a measurement in one of the following two categories: High: ≥120 with an increase from baseline ≥15 beats per minute (bpm) Low: ≤50 with a decrease from baseline ≥15 bpm
Time frame: Baseline, 52 Weeks
Population: Safety Set includes all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | High | 1.8 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | Low | 0.0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | High | 0.0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | Low | 1.8 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | High | 3.6 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate | Low | 0.0 Percentage of participants |
Secondary
Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure
Systolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes. A Notably Abnormal Systolic Blood Pressure was defined as a measurement in one of the following two categories: High: ≥180 with an increase from baseline ≥20 mmHg Low: ≤90 with a decrease from baseline ≥20 mmHg
Time frame: Baseline, 52 Weeks
Population: Safety Set includes all randomized participants who received treatment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | High | 0.0 Percentage of participants |
| 5 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | Low | 10.9 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | High | 0.0 Percentage of participants |
| 10 mg/kg/Day Deferasirox | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | Low | 5.5 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | High | 1.8 Percentage of participants |
| Placebo | Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure | Low | 16.1 Percentage of participants |
Secondary
Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter
Blood was collected for serum ferritin at Core Baseline and monthly during the Eighth quarter of the Extension Study. Absolute change from Baseline: quarterly average - baseline average. A negative change from baseline indicated improvement.
Time frame: Core Baseline, Eighth Quarter (last 3 months of the study)
Population: Full Analysis Set included all randomized participants. Only patients with a value both at baseline and at considered time point are included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter | -565.9 micrograms/liter | Standard Deviation 504.25 |
| 10 mg/kg/Day Deferasirox | Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter | -504.3 micrograms/liter | Standard Deviation 770.6 |
Secondary
Extension Study: Change From Baseline in Hemoglobin at Month 24
Blood was collected for Hemoglobin at Baseline and Month 24. Change from Baseline= Month 24 hemoglobin - Baseline hemoglobin.
Time frame: Core Baseline, Month 24
Population: Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Change From Baseline in Hemoglobin at Month 24 | -2.6 g/L | 95% Confidence Interval 6.07 |
| 10 mg/kg/Day Deferasirox | Extension Study: Change From Baseline in Hemoglobin at Month 24 | -3.1 g/L | 95% Confidence Interval 9.48 |
Secondary
Extension Study: Change From Baseline in Transferrin Saturation at Month 24
Blood was collected for transferrin saturation at Baseline and Month 24. Change from baseline= Month 24 transferrin saturation - baseline transferrin saturation.
Time frame: Core Baseline, Month 24
Population: Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Change From Baseline in Transferrin Saturation at Month 24 | -5.01 Percent saturation | 95% Confidence Interval 24.36 |
| 10 mg/kg/Day Deferasirox | Extension Study: Change From Baseline in Transferrin Saturation at Month 24 | 1.35 Percent saturation | 95% Confidence Interval 13.01 |
Secondary
Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
LIC was measured by magnetic resonance imaging technique at Baseline and Month 24. A negative change from baseline indicated improvement.
Time frame: Core Baseline, Month 24
Population: Full Analysis Set. The last available post-baseline LIC was carried forward if no LIC value was available at Week 52. Only patients with both baseline and at least one post-baseline value were included for this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | -7.1 mg iron (Fe)/g dry weight (dw) | Standard Deviation 5.3 |
| 10 mg/kg/Day Deferasirox | Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24 | -6.7 mg iron (Fe)/g dry weight (dw) | Standard Deviation 6.67 |
Secondary
Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for serum ferritin difference from Baseline at Month 24 versus LIC difference from Baseline at Month 24. A value of 1.0 indicates a perfect correlation.
Time frame: Core Baseline, Month 24
Population: Participants from the Extension Full Analysis Set (all randomized participants)in the Extension Study with data available for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 5 mg/kg/Day Deferasirox | Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration) | 0.735 Correlation coefficient |