THALASSA: Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload and a One Year Open-label Extension Study

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00873041
• Collaborator: (none)
• Enrollment: 166
• Locations: 21
• Arms: 4
• Duration (Months): 43
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Non-transfusion Dependent Thalassemia	Drug: deferasirox; Drug: placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 166 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Jun 1, 2011
• Actual Study Completion Date: Jun 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: deferasirox; Supplied as 125 mg, 250 mg and 500 mg tablets.; Drug: placebo; Supplied as matching 125 mg, 250 mg and 500 mg tablets.
Experimental: 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.	Drug: deferasirox; Supplied as 125 mg, 250 mg and 500 mg tablets.; Drug: placebo; Supplied as matching 125 mg, 250 mg and 500 mg tablets.
Placebo Comparator: 5 mg/kg/day placebo Placebo tablet matching 5 mg/kg/day orally in the morning each day 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.	Drug: placebo; Supplied as matching 125 mg, 250 mg and 500 mg tablets.
Placebo Comparator: 10 mg/kg/day placebo Placebo tablet matching 10 mg/kg/day orally in the morning each day 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.	Drug: placebo; Supplied as matching 125 mg, 250 mg and 500 mg tablets.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

10. 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)

11. 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

12. 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

13. 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

14. 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.

15. 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.

16. 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.

17. 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.

18. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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 Exclusion Criteria:

• Patients with a continuous increase in serum creatinine ≥ 33% above the baseline value and > ULN who did not improve after drug interruption or dose reduction in the core study

• Patients with a continuous increase in ALT greater than 2 times the baseline value and

5 times ULN who did not improve after drug interruption or dose reduction in the core study

• Patients with progressive proteinuria, as assessed by the investigator, who did not improve after drug interruption or dose reduction in the core study

• Significant medical condition interfering with the ability to partake in this study (e.g.systemic uncontrolled hypertension, unstable cardiac disease not controlled by standard medical therapy, systemic disease (cardiovascular, renal, hepatic, etc.)

Other protocol-defined inclusion/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital & Research Center Oakland	Oakland	California	United States	94609-1809
2	Children's Memorial Hospital/Division of Hematology/Oncology	Chicago	Illinois	United States	60614-3394
3	New York Presbyterian Hospital/Weill Medical College of Cornell University	New York	New York	United States	10021
4	Novartis Investigative Site	Athens		Greece
5	Novartis Investigative Site	Patras		Greece
6	Novartis Investigative Site	Thessaloniki		Greece
7	Novartis Investigative Site	Cagliari		Italy
8	Novartis Investigative Site	Genova		Italy
9	Novartis Investigative Site	Milano		Italy
10	Novartis Investigative Site	Napoli		Italy
11	Novartis Investigative Site	Rome		Italy
12	Novartis Investigative Site	Beirut		Lebanon
13	Novartis Investigative Site	Ampang Selangor		Malaysia
14	Novartis Investigative Site	Kuala Lumpur		Malaysia
15	Novartis Investigative Site	Taipei		Taiwan
16	Novartis Investigative Site	Bangkok		Thailand
17	Novartis Investigative Site	Adana		Turkey
18	Novartis Investigative Site	Ankara		Turkey
19	Novartis Investigative Site	Istanbul		Turkey
20	Novartis Investigative Site	Izmir		Turkey
21	Novartis Investigative Site	London		United Kingdom

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Visit NovartisClinicalTrials.com: Pre-qualify for a trial, and view a list of trials and participating study centers.

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00873041
• Other Study ID Numbers: CICL670A2209; EudraCT 2007-007000-15; NCT01185106
• First Posted: Apr 1, 2009
• Last Update Posted: Jul 9, 2013
• Last Verified: May 1, 2013

• Keywords provided by Novartis Pharmaceuticals: Thalassemia; thalassemia intermedia; alpha-thalassemia; beta-thalassemia; deferasirox; iron overload; non-transfusion dependent
• Additional relevant MeSH terms: Thalassemia; Iron Overload; Deferasirox

Study Results

Participant Flow

Pre-assignment Detail	There was a 4 week screening period to determine eligibility prior to randomization.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo/Deferasirox
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Period Title: Core Study
STARTED	55	55	56
COMPLETED	48	49	51
NOT COMPLETED	7	6	5
Period Title: Core Study
STARTED	41	44	48
COMPLETED	40	44	46
NOT COMPLETED	1	0	2

Baseline Characteristics

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo	Total
Arm/Group Description	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.	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.	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.	Total of all reporting groups
Overall Participants	55	55	56	166
Age, Customized (Number) [Number]
<18 years	6 10.9%	7 12.7%	8 14.3%	21 12.7%
Between 18 and 65 years	49 89.1%	47 85.5%	48 85.7%	144 86.7%
>=65 years	0 0%	1 1.8%	0 0%	1 0.6%
Sex: Female, Male (Count of Participants)
Female	26 47.3%	26 47.3%	25 44.6%	77 46.4%
Male	29 52.7%	29 52.7%	31 55.4%	89 53.6%

Outcome Measures

1. Secondary Outcome

Title	Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	49	48	51
Least Squares Mean (Standard Error) [mg iron (Fe)/g dry weight (dw)]	-0.87 (0.448)	-0.90 (0.450)	-0.24 (0.439)

2. Secondary Outcome

Title	Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter
Description	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])

Outcome Measure Data

Analysis Population Description

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/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	51	50	53
Mean (Standard Deviation) [μg/L]	-130.47 (260.555)	-249.16 (389.356)	128.63 (249.689)

3. Secondary Outcome

Title	Core Study: Change in Serum Ferritin Between Baseline and Second Quarter
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	52	54	56
Mean (Standard Deviation) [μg/L]	8.20 (244.443)	-17.75 (368.812)	106.45 (330.217)

4. Secondary Outcome

Title	Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe
Description	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

Outcome Measure Data

Analysis Population Description

Safety Analysis Set included all randomized participants who received treatment.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	55	55	56
Mild	36.4 66.2%	43.6 79.3%	42.9 76.6%
Moderate	27.3 49.6%	16.4 29.8%	21.4 38.2%
Severe	12.7 23.1%	18.2 33.1%	16.1 28.8%

5. Secondary Outcome

Title	Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	26	25	30
Change from baseline at Week 24 (n=26,24,30)	0.56 (2.992)	0.69 (3.131)	0.94 (2.693)
Change from baseline at Week 52	-1.82 (3.101)	-4.02 (4.849)	0.62 (4.128)

6. Secondary Outcome

Title	Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
Description	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

Outcome Measure Data

Analysis Population Description

Participants from the Full Analysis Set (all randomized participants).

Arm/Group Title	All Randomized Participants
Arm/Group Description	Participants received a starting dose of 5 mg/kg/day or 10 mg/kg/day deferasirox tablets or matching placebo 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.
Measure Participants	165
Baseline	0.653
Week 52 (n=134)	0.609

7. Secondary Outcome

Title	Core Study: Change From Baseline in Hemoglobin at Month 12
Description	Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin.
Time Frame	Baseline, Month 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	47	48	49
Mean (Standard Deviation) [g/L]	-1.8 (5.45)	-0.7 (6.27)	-2.8 (7.31)

8. Secondary Outcome

Title	Core Study: Change From Baseline in Transferrin Saturation at Month 12
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	47	47	47
Mean (Standard Deviation) [Percent saturation]	-3.79 (14.234)	-3.64 (22.443)	3.37 (10.083)

9. Secondary Outcome

Title	Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Placebo
Arm/Group Description	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	54
Mean (Standard Deviation) [mg iron (Fe)/g dry weight (dw)]	0.26 (3.501)

10. Secondary Outcome

Title	Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results
Description	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

Outcome Measure Data

Analysis Population Description

Safety Set included all randomized participants who received treatment.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	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 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.
Measure Participants	55	55	56
Platelet count	5.5 10%	5.5 10%	10.7 19.1%
Absolute neutrophils	5.5 10%	3.6 6.5%	5.4 9.6%
ALT	0 0%	0 0%	1.8 3.2%
AST	0 0%	1.8 3.3%	1.8 3.2%
Serum creatinine	0 0%	5.5 10%	0 0%
Creatinine clearance	1.8 3.3%	1.8 3.3%	0 0%
Urinary protein/creatinine ratio	1.8 3.3%	0 0%	0 0%

11. Primary Outcome

Title	Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	51	54	54
Least Squares Mean (Standard Error) [mg iron (Fe)/g dry weight (dw)]	-1.95 (0.500)	-3.80 (0.484)	0.38 (0.486)

12. Secondary Outcome

Title	Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure
Description	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

Outcome Measure Data

Analysis Population Description

Safety Set includes all randomized participants who received treatment.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	55	55	56
High	0.0 0%	0.0 0%	1.8 3.2%
Low	10.9 19.8%	5.5 10%	16.1 28.8%

13. Secondary Outcome

Title	Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure
Description	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

Outcome Measure Data

Analysis Population Description

Safety Set includes all randomized participants who received treatment.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	55	55	56
High	0.0 0%	0.0 0%	0.0 0%
Low	14.5 26.4%	10.9 19.8%	14.3 25.5%

14. Secondary Outcome

Title	Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate
Description	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

Outcome Measure Data

Analysis Population Description

Safety Set includes all randomized participants who received treatment.

Arm/Group Title	5 mg/kg/Day Deferasirox	10 mg/kg/Day Deferasirox	Placebo
Arm/Group Description	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.	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.	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.
Measure Participants	55	55	56
High	1.8 3.3%	0.0 0%	3.6 6.4%
Low	0.0 0%	1.8 3.3%	0.0 0%

15. Secondary Outcome

Title	Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter
Description	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)

Outcome Measure Data

Analysis Population Description

Full Analysis Set included all randomized participants. Only patients with a value both at baseline and at considered time point are included.

Arm/Group Title	Deferasirox	Placebo/Deferasirox
Arm/Group Description	Participants received a starting dose of 5 mg/kg/day 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. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	84	46
Mean (Standard Deviation) [micrograms/liter]	-565.9 (504.25)	-504.3 (770.60)

16. Primary Outcome

Title	Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Deferasirox	Placebo/Deferasirox
Arm/Group Description	Participants received a starting dose of 5 mg/kg/day 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. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	110	56
Number (95% Confidence Interval) [Percentage of participants]	39.1 71.1%	37.5 68.2%

17. Secondary Outcome

Title	Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Deferasirox	Placebo/Deferasirox
Arm/Group Description	Participants received a starting dose of 5 mg/kg/day 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. In the Extension Study participants received deferasirox once daily (dose based on LIC) for 52 weeks.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	84	46
Mean (Standard Deviation) [mg iron (Fe)/g dry weight (dw)]	-7.1 (5.3)	-6.7 (6.67)

18. Secondary Outcome

Title	Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)
Description	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

Outcome Measure Data

Analysis Population Description

Participants from the Extension Full Analysis Set (all randomized participants)in the Extension Study with data available for analysis.

Arm/Group Title	All Randomized Participants
Arm/Group Description	Participants received a starting dose of 5 mg/kg/day or 10 mg/kg/day deferasirox tablets or matching placebo 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.
Measure Participants	129
Number [Correlation coefficient]	0.735

19. Secondary Outcome

Title	Extension Study: Change From Baseline in Hemoglobin at Month 24
Description	Blood was collected for Hemoglobin at Baseline and Month 24. Change from Baseline= Month 24 hemoglobin - Baseline hemoglobin.
Time Frame	Core Baseline, Month 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (all randomized participants). Only patients with a value both at baseline and at considered timepoint are included in analyses.

Arm/Group Title	Deferasirox	Placebo/Deferasirox
Arm/Group Description	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	59	29
Mean (95% Confidence Interval) [g/L]	-2.6 (6.07)	-3.1 (9.48)

20. Secondary Outcome

Title	Extension Study: Change From Baseline in Transferrin Saturation at Month 24
Description	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

Outcome Measure Data

Analysis Population Description

Full Analysis Set (all randomized patients). Only patients with a value both at baseline and at considered timepoint are included in the analyses.

Arm/Group Title	Deferasirox	Placebo/Deferasirox
Arm/Group Description	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.	Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
Measure Participants	66	33
Mean (95% Confidence Interval) [Percent saturation]	-5.01 (24.36)	1.35 (13.01)

Adverse Events

Arm/Group Title	Deferasirox 5 mg/kg/Day		Deferasirox 10 mg/kg/Day		Placebo/Deferasirox Any Dose
Arm/Group Description	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.		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.		Placebo tablet matching 5 mg/kg/day or 10 mg/kg/day orally in the morning each day 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.
All Cause Mortality
	Deferasirox 5 mg/kg/Day		Deferasirox 10 mg/kg/Day		Placebo/Deferasirox Any Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Deferasirox 5 mg/kg/Day		Deferasirox 10 mg/kg/Day		Placebo/Deferasirox Any Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/55 (20%)		12/55 (21.8%)		16/56 (28.6%)
Blood and lymphatic system disorders
Anaemia	1/55 (1.8%)		2/55 (3.6%)		3/56 (5.4%)
Haemolysis	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Cardiac disorders
Arrhythmia	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Atrial fibrillation	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Congenital, familial and genetic disorders
Atrial septal defect	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Eye disorders
Cataract	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Gastrointestinal disorders
Abdominal pain	1/55 (1.8%)		1/55 (1.8%)		0/56 (0%)
Abdominal tenderness	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Duodenal ulcer	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Food poisoning	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Gastritis	0/55 (0%)		2/55 (3.6%)		0/56 (0%)
Pancreatitis acute	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
General disorders
Pyrexia	1/55 (1.8%)		3/55 (5.5%)		1/56 (1.8%)
Hepatobiliary disorders
Cholangitis	0/55 (0%)		1/55 (1.8%)		1/56 (1.8%)
Cholecystitis	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Cholecystitis acute	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Cholecystitis chronic	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Cholelithiasis	0/55 (0%)		1/55 (1.8%)		1/56 (1.8%)
Hepatitis	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Hepatotoxicity	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Portal vein thrombosis	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Infections and infestations
Babesiosis	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Cellulitis	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Dengue fever	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Gastroenteritis	3/55 (5.5%)		4/55 (7.3%)		2/56 (3.6%)
Helicobacter gastritis	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Influenza	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Liver abscess	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Osteomyelitis	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Pneumonia	0/55 (0%)		0/55 (0%)		2/56 (3.6%)
Respiratory tract infection	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Viral upper respiratory tract infection	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Injury, poisoning and procedural complications
Ligament rupture	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Lower limb fracture	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Meniscus lesion	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Pelvic fracture	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Road traffic accident	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Tibia fracture	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Upper limb fracture	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Investigations
C-reactive protein	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Weight decreased	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Metabolism and nutrition disorders
Dehydration	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Nervous system disorders
Optic neuritis	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Syncope	1/55 (1.8%)		0/55 (0%)		0/56 (0%)
Reproductive system and breast disorders
Ovarian cyst ruptured	0/55 (0%)		0/55 (0%)		1/56 (1.8%)
Skin and subcutaneous tissue disorders
Pruritus	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Rash	0/55 (0%)		1/55 (1.8%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Deferasirox 5 mg/kg/Day		Deferasirox 10 mg/kg/Day		Placebo/Deferasirox Any Dose
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/55 (67.3%)		45/55 (81.8%)		48/56 (85.7%)
Blood and lymphatic system disorders
Anaemia	6/55 (10.9%)		4/55 (7.3%)		3/56 (5.4%)
Eye disorders
Conjunctivitis	3/55 (5.5%)		1/55 (1.8%)		1/56 (1.8%)
Gastrointestinal disorders
Abdominal pain	4/55 (7.3%)		4/55 (7.3%)		9/56 (16.1%)
Abdominal pain upper	4/55 (7.3%)		9/55 (16.4%)		7/56 (12.5%)
Constipation	0/55 (0%)		0/55 (0%)		3/56 (5.4%)
Diarrhoea	8/55 (14.5%)		7/55 (12.7%)		12/56 (21.4%)
Dyspepsia	1/55 (1.8%)		3/55 (5.5%)		2/56 (3.6%)
Food poisoning	0/55 (0%)		3/55 (5.5%)		4/56 (7.1%)
Gastritis	3/55 (5.5%)		1/55 (1.8%)		2/56 (3.6%)
Nausea	5/55 (9.1%)		9/55 (16.4%)		12/56 (21.4%)
Tooth disorder	0/55 (0%)		0/55 (0%)		3/56 (5.4%)
Vomiting	4/55 (7.3%)		3/55 (5.5%)		8/56 (14.3%)
General disorders
Asthenia	2/55 (3.6%)		1/55 (1.8%)		3/56 (5.4%)
Fatigue	3/55 (5.5%)		7/55 (12.7%)		6/56 (10.7%)
Oedema peripheral	1/55 (1.8%)		1/55 (1.8%)		4/56 (7.1%)
Pain	3/55 (5.5%)		0/55 (0%)		1/56 (1.8%)
Pyrexia	10/55 (18.2%)		5/55 (9.1%)		15/56 (26.8%)
Infections and infestations
Gastroenteritis	3/55 (5.5%)		5/55 (9.1%)		4/56 (7.1%)
Gastroenteritis viral	0/55 (0%)		3/55 (5.5%)		2/56 (3.6%)
Influenza	4/55 (7.3%)		6/55 (10.9%)		5/56 (8.9%)
Nasopharyngitis	6/55 (10.9%)		5/55 (9.1%)		6/56 (10.7%)
Pharyngitis	6/55 (10.9%)		2/55 (3.6%)		2/56 (3.6%)
Rhinitis	2/55 (3.6%)		5/55 (9.1%)		3/56 (5.4%)
Tonsillitis	5/55 (9.1%)		3/55 (5.5%)		5/56 (8.9%)
Upper respiratory tract infection	9/55 (16.4%)		14/55 (25.5%)		14/56 (25%)
Viral infection	2/55 (3.6%)		0/55 (0%)		4/56 (7.1%)
Investigations
Blood creatinine increased	1/55 (1.8%)		3/55 (5.5%)		2/56 (3.6%)
Heart rate increased	0/55 (0%)		0/55 (0%)		3/56 (5.4%)
Metabolism and nutrition disorders
Decreased appetite	3/55 (5.5%)		1/55 (1.8%)		3/56 (5.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	3/55 (5.5%)		2/55 (3.6%)		5/56 (8.9%)
Back pain	2/55 (3.6%)		1/55 (1.8%)		6/56 (10.7%)
Flank pain	1/55 (1.8%)		0/55 (0%)		3/56 (5.4%)
Pain in extremity	2/55 (3.6%)		2/55 (3.6%)		3/56 (5.4%)
Nervous system disorders
Dizziness	4/55 (7.3%)		0/55 (0%)		1/56 (1.8%)
Headache	3/55 (5.5%)		11/55 (20%)		12/56 (21.4%)
Psychiatric disorders
Insomnia	1/55 (1.8%)		3/55 (5.5%)		4/56 (7.1%)
Respiratory, thoracic and mediastinal disorders
Cough	3/55 (5.5%)		4/55 (7.3%)		8/56 (14.3%)
Dyspnoea	1/55 (1.8%)		1/55 (1.8%)		3/56 (5.4%)
Epistaxis	3/55 (5.5%)		1/55 (1.8%)		0/56 (0%)
Oropharyngeal pain	4/55 (7.3%)		7/55 (12.7%)		3/56 (5.4%)
Skin and subcutaneous tissue disorders
Rash	3/55 (5.5%)		6/55 (10.9%)		5/56 (8.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.