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

Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT01709838
Collaborator
(none)
134
Enrollment
11
Locations
1
Arm
73.4
Actual Duration (Months)
12.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Assessed the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 52 weeks of treatment. Provided further assessment of the long-term efficacy and safety of deferasirox in NTDT patients with iron overload (LIC ≥ 5 mg Fe/g liver dw and SF ≥ 300 ng/mL) for up to 260 weeks.

Condition or DiseaseIntervention/TreatmentPhase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
134 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open Label, Multi-center, Efficacy and Safety Study of Deferasirox in Iron Overloaded Patients With Non-transfusion Dependent Thalassemia
Actual Study Start Date :
Dec 6, 2012
Actual Primary Completion Date :
Jan 3, 2015
Actual Study Completion Date :
Jan 17, 2019

Arms and Interventions

ArmIntervention/Treatment
Other: Deferasirox

All patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).

Drug: deferasirox
Deferasirox dispersible tablets at strengths of 125 mg, 250 mg, and 500 mg were administered by oral daily dosing.
Other Names:
  • ICL670
  • Outcome Measures

    Primary Outcome Measures

    1. Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline [Baseline, 52 weeks]

      Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment

    Secondary Outcome Measures

    1. Percentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw [5 years]

      The percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study

    2. Time to Achieving LIC <5 mg Fe/g dw [5 years]

      Time to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 mg Fe/g dw during the study

    3. Time From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period [post-baseline, up to 260 weeks]

      Time from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period

    4. Absolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2) [Baseline, 52, 104 & 156 Weeks]

      The SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].

    5. Absolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™) [Baseline, 52, 104 & 156 Weeks]

      The PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].

    6. Absolute Change in LIC From Baseline Over Time [24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks]

      Absolute change in serum ferritin from baseline over time up to 260 weeks

    7. Serum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up) [Baseline, End of Study (EOS): Week 260 + 30 days follow up]

      Correlation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.

    8. Correlation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up) [Week 24, End of Study (EOS): Week 260 + 30 days follow up]

      Correlation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.

    9. Absolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome [Baseline, 52 Weeks]

      Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)

    10. Absolute Change in Serum Ferritin From Baseline After 52 Weeks [Baseline, 52 weeks]

      Absolute change in serum ferritin from baseline after 52 weeks of treatment

    11. PK Parameters: AUCtau [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

      The pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).

    12. PK Parameters: Cmax [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

      The pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume

    13. PK Parameters: Tmax [pre-dose (0 hour), and at 2, and 4 hours at Week 4]

      The pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.

    14. Plasma Pharmacokinetics (PK) Deferasirox Concentrations [Weeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose]

      Blood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.

    Eligibility Criteria

    Criteria

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

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

    Exclusion Criteria:

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

    Pediatrics Only:

    A patient's weight of at least 20 kg is required to allow dosing of 5 mg/kg with one tablet of 125 mg

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Novartis Investigative SiteNanningGuangxiChina530021
    2Novartis Investigative SiteGoudi-AthensGRGreece115 27
    3Novartis Investigative SiteCagliariCAItaly09121
    4Novartis Investigative SiteMilanoMIItaly20122
    5Novartis Investigative SiteHazmiyehBeirutLebanonPO BOX 213
    6Novartis Investigative SiteBangkokThailand10700
    7Novartis Investigative SiteTunisTunisia1006
    8Novartis Investigative SiteAdanaTurkey01330
    9Novartis Investigative SiteIstanbulTurkey34093
    10Novartis Investigative SiteIzmirTurkey35040
    11Novartis Investigative SiteLondonUnited KingdomNW1 2PJ

    Sponsors and Collaborators

    • Novartis Pharmaceuticals

    Investigators

    • Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01709838
    Other Study ID Numbers:
    • CICL670E2419
    • 2012-000650-64
    First Posted:
    Oct 18, 2012
    Last Update Posted:
    Oct 2, 2019
    Last Verified:
    Sep 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Novartis Pharmaceuticals
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsAt least 117 patients were planned to be enrolled; 134 patients were enrolled.
    Pre-assignment DetailAt least 117 patients were planned to be enrolled; 134 patients were enrolled.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Period Title: Overall Study
    STARTED134
    COMPLETED67
    NOT COMPLETED67

    Baseline Characteristics

    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Overall Participants134
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    28.0
    (11.10)
    Age, Customized (participants) [Number]
    < 18 years
    25
    18.7%
    18 - < 50 years
    104
    77.6%
    50 - < 65 years
    5
    3.7%
    Sex: Female, Male (Count of Participants)
    Female
    58
    43.3%
    Male
    76
    56.7%
    Race/Ethnicity, Customized (Number) [Number]
    Asian
    85
    63.4%
    Caucasian
    48
    35.8%
    Other
    1
    0.7%

    Outcome Measures

    1. Primary Outcome
    TitleAbsolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline
    DescriptionAbsolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment
    Time FrameBaseline, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Mean (Standard Deviation) [mg Fe/g dw]
    -6.68
    (7.018)
    2. Secondary Outcome
    TitlePercentage of Participants With Baseline LIC>15 Achieving LIC<5 mg Fe/g dw
    DescriptionThe percentage of participants with baseline LIC>15 mg Fe/g dw achieving an LIC <5 mg Fe/g dw during the study
    Time Frame5 years

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Number [percentage of participants]
    51.0
    38.1%
    3. Secondary Outcome
    TitleTime to Achieving LIC <5 mg Fe/g dw
    DescriptionTime to achieving LIC <5 mg Fe/g dw for participants with baseline LIC>15 mg Fe/g dw during the study
    Time Frame5 years

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Median (95% Confidence Interval) [months]
    36.3
    4. Secondary Outcome
    TitleTime From Target LIC of 3 mg Fe/g dw to the First LIC ≥5 mg Fe/g dw in the Follow up Period
    DescriptionTime from the target LIC <3 mg Fe/g dw to the first LIC ≥5 mg Fe/g dw in the follow-up period
    Time Framepost-baseline, up to 260 weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Median (95% Confidence Interval) [days]
    27.4
    5. Secondary Outcome
    TitleAbsolute Change in Health-related Outcomes Using Medical Outcomes Study Form 36 (SF-36v2)
    DescriptionThe SF-36 is a self-administered questionnaire for adults (from 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, General health perceptions, Vitality, Social functioning, Role limitations due to emotional problems and General mental health . The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].
    Time FrameBaseline, 52, 104 & 156 Weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants105
    Physical Functioning Week 52
    -0.5
    (5.5)
    Physical Functioning Week 104
    -0.7
    (4.9)
    Physical Functioning Week 156
    0.6
    (6.1)
    Role Physical Week 52
    0.9
    (9.1)
    Role Physical Week 104
    -1.0
    (10.2)
    Role Physical Week 156
    1.0
    (10.9)
    Bodily Pain Week 52
    -0.0
    (11.6)
    Bodily Pain Week 104
    -1.3
    (10.8)
    General Health Week 52
    -2.3
    (9.1)
    Bodily Pain Week 156
    0.9
    (12.2)
    General Health Pain Week 104
    -1.9
    (9.2)
    General Health Week 156
    -1.1
    (8.6)
    Vitality Week 52
    1.1
    (9.7)
    Vitality Week 104
    -0.2
    (8.7)
    Vitality Week 156
    2.1
    (9.6)
    Social Functioning Week 52
    0.9
    (9.8)
    Social Functioning Week 104
    -1.2
    (9.6)
    Social Functioning Week 156
    1.6
    (10.6)
    Role Emotional Week 52
    -0.1
    (11.3)
    Role Emotional Week 104
    -2.5
    (12.2)
    Role Emotional Week 156
    0.7
    (11.2)
    Mental Health Week 52
    1.5
    (11.7)
    Mental Health Week 104
    -0.6
    (11.4)
    Mental Health Week 156
    2.8
    (10.9)
    Physical Component Week 52
    -0.8
    (7.2)
    Physical Component Week 104
    -1.0
    (7.4)
    Physical Component Week 156
    -0.1
    (7.9)
    Mental Component Week 104
    -1.3
    (11.1)
    Mental Component Week 52
    1.1
    (10.9)
    Mental Component Week 156
    2.2
    (10.8)
    SF6D Health Utility Index Week 52
    0.0
    (0.1)
    SF6D Health Utility Index Week 104
    -0.0
    (0.1)
    SF6D Health Utility Index Week 156
    0.0
    (0.1)
    6. Secondary Outcome
    TitleAbsolute Change in Health-related Outcomes Using the Pediatric Quality of Life Questionnaire (PedsQL™)
    DescriptionThe PedsQL™ is a modular approach to measuring health-related quality of life (HRQOL) in children and adolescents. The 23-item PedsQL™ Generic Core Scales encompass the essential core domains for pediatric HRQOL measurement: 1) Physical Functioning (8 items), 2) Emotional Functioning (5 items), 3) Social Functioning (5 items), and 4) School Functioning (5 items). The Generic Core Scales are designed to enable comparisons across patient and healthy populations. The higher values indicate a better evaluation of health. Range: 0 to 100 [0 (worst possible health state measured by the questionnaire) to 100 (best possible health state)].
    Time FrameBaseline, 52, 104 & 156 Weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants16
    Physical Functioning - Teenager Wk 52
    2.3
    (13.7)
    Physical Functioning - Teenager Wk 104
    1.0
    (19.3)
    Physical Functioning - Teenager Wk 156
    -0.9
    (15.4)
    Emotional Functioning - Teenager Wk 52
    0.7
    (17.8)
    Emotional Functioning - Teenager Wk 104
    3.1
    (27.6)
    Emotional Functioning - Teenager Wk 156
    10.9
    (25.9)
    Social Functioning - Teenager Wk 52
    -9.3
    (17.5)
    Social Functioning - Teenager Wk 104
    -10.0
    (17.8)
    Social Functioning - Teenager Wk 156
    -5.0
    (20.1)
    School Functioning - Teenager Wk 52
    0.7
    (12.4)
    School Functioning - Teenager Wk 104
    -3.8
    (16.4)
    School Functioning - Teenager Wk 156
    1.0
    (21.4)
    Physical Health - Teenager Wk 52
    2.3
    (13.7)
    Physical Health - Teenager Wk 104
    1.0
    (19.3)
    Physical Health - Teenager Wk 156
    -0.9
    (15.4)
    Psychosocial Health - Teenager Wk 52
    -3.3
    (13.0)
    Psychosocial Health - Teenager Wk 104
    -4.0
    (16.9)
    Psycholosocial Health - Teenager Wk 156
    2.0
    (19.1)
    Total Score - Teenager Wk 52
    -1.0
    (10.6)
    Total Score - Teenager Wk 104
    -1.9
    (14.4)
    Total Score - Teenager Wk 156
    1.2
    (15.8)
    Physical Functioning - Parent Wk 52
    -2.9
    (19.0)
    Physical Functioning - Parent Wk 104
    0.0
    (18.6)
    Physical Functioning - Parent Wk 156
    -0.3
    (15.6)
    Emotional Functioning - Parent Wk 52
    -8.7
    (19.1)
    Emotional Functioning - Parent Wk 104
    -3.8
    (20.8)
    Emotional Functioning - Parent Wk 156
    2.0
    (20.6)
    Social Functioning - Parent Wk 52
    -3.7
    (15.5)
    Social Functioning - Parent Wk 104
    -4.6
    (18.0)
    Social Functioning - Parent Wk 156
    -6.0
    (20.9)
    School Functioning - Parent Wk 52
    -3.6
    (20.6)
    School Functioning - Parent Wk 104
    0.0
    (11.7)
    School Functioning - Parent Wk 156
    -0.6
    (21.1)
    Physical Health - Parent Wk 52
    -2.9
    (19.0)
    Physical Health - Parent Wk 104
    0.0
    (18.6)
    Physical Health - Parent Wk 156
    -0.3
    (15.6)
    Psychosocial Health - Parent Wk 52
    -5.5
    (15.0)
    Psychosocial Health - Parent Wk 104
    -3.2
    (12.3)
    Psychosocial Health - Parent Wk 156
    -1.8
    (14.1)
    Total Score - Parent Wk 52
    -4.6
    (14.8)
    Total Score - Parent Wk 104
    -1.9
    (12.0)
    Total Score - Parent Wk 156
    -1.1
    (12.9)
    7. Secondary Outcome
    TitleAbsolute Change in LIC From Baseline Over Time
    DescriptionAbsolute change in serum ferritin from baseline over time up to 260 weeks
    Time Frame24, 52, 76, 104, 128, 156, 180, 208, 232, 260 Weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Week 24
    -3.67
    (3.778)
    Week 52
    -7.02
    (7.132)
    Week 76
    -8.93
    (8.922)
    Week 104
    -9.63
    (9.474)
    Week 128
    -10.03
    (9.445)
    Week 156
    -10.20
    (9.746)
    Week 180
    -9.94
    (9.838)
    Week 208
    -10.04
    (10.010)
    Week 232
    -10.58
    (10.045)
    Week 260
    -10.57
    (10.366)
    8. Secondary Outcome
    TitleSerum Ferritin (SF) vs LIC at Baseline and EOS (Week 260 + 30 Days Follow-up)
    DescriptionCorrelation between serum ferritin and LIC is assessed using scatter plots with pearson correlation coefficient and simple linear model.
    Time FrameBaseline, End of Study (EOS): Week 260 + 30 days follow up

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    At Baseline
    0.730
    Change from Baseline at EOS
    0.531
    9. Secondary Outcome
    TitleCorrelation Analysis for Absolute Change in LIC and Serum Ferritin at Week 24 and EOS (Week 260 + 30 Days Follow-up)
    DescriptionCorrelation for absolute change between LIC and serum ferritin was assessed using scatter plots with pearson correlation coefficient and simple linear model.
    Time FrameWeek 24, End of Study (EOS): Week 260 + 30 days follow up

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Week 24
    0.299
    Change from Baseline at EOS
    0.740
    10. Secondary Outcome
    TitleAbsolute Change in LIC From Baseline After 52 Weeks of Treatment by Underlying Non-transfusion Dependent Thalassemia (NTDT) Syndrome
    DescriptionAbsolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment by underlying NTDT syndrome. The 4 underlying disease types: Beta-thalassemia intermedia (N =69), HbE beta-thalassemia (N = 24), Alpha-thalassemia intermedia (HbH disease) (N = 40), Other, specify (N = 1)
    Time FrameBaseline, 52 Weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Beta-thalassemia intermedia
    -6.11
    (6.481)
    HbE beta-thalassemia
    -6.18
    (7.572)
    Alpha-thalassemia intermedia (HbH disease)
    -7.97
    (7.652)
    Other, specify
    -6.00
    (NA)
    11. Secondary Outcome
    TitleAbsolute Change in Serum Ferritin From Baseline After 52 Weeks
    DescriptionAbsolute change in serum ferritin from baseline after 52 weeks of treatment
    Time FrameBaseline, 52 weeks

    Outcome Measure Data

    Analysis Population Description
    The Full Analysis Set (FAS) consisted of all patients who were assigned at least one dose of study drug.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants134
    Mean (Standard Deviation) [ng/mL]
    -494.64
    (760.782)
    12. Secondary Outcome
    TitlePK Parameters: AUCtau
    DescriptionThe pharmacokinetic parameter, AUCtau was determined using non-compartmental method(s) for deferasirox and its iron complex. AUC=area under the concentration-time curve during a dosing interval at steady state (amount × time × volume).
    Time Framepre-dose (0 hour), and at 2, and 4 hours at Week 4

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all patients from FAS who had evaluable PK data.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants22
    Geometric Mean (Geometric Coefficient of Variation) [hr*umol/L]
    678.2
    (61.9)
    13. Secondary Outcome
    TitlePK Parameters: Cmax
    DescriptionThe pharmacokinetic parameter, Cmax, was determined using non-compartmental method(s) for deferasirox and its iron complex. Cmax (maximum/peak plasma drug concentration after drug administration)=amount × volume
    Time Framepre-dose (0 hour), and at 2, and 4 hours at Week 4

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all patients from FAS who had evaluable PK data.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants22
    Geometric Mean (Geometric Coefficient of Variation) [umol/L]
    53.367
    (60.960)
    14. Secondary Outcome
    TitlePK Parameters: Tmax
    DescriptionThe pharmacokinetic parameter, Tmax, may be determined using non-compartmental method(s) for deferasirox and its iron complex. Tmax=time to reach maximum/peak concentration following drug administration.
    Time Framepre-dose (0 hour), and at 2, and 4 hours at Week 4

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all patients from FAS who had evaluable PK data.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants22
    Geometric Mean (Geometric Coefficient of Variation) [hr]
    2.5131
    (33.9321)
    15. Secondary Outcome
    TitlePlasma Pharmacokinetics (PK) Deferasirox Concentrations
    DescriptionBlood samples for PK evaluation were collected for a sub-group of patients. The patient had to have been on treatment without dose adjustment or treatment interruption (for any reason) for at least 4 consecutive days prior to scheduled PK sampling visit. If there was a dosage change or interruption within 4 days of the visit, no PK blood samples was collected, and an appropriate comment had to be made on the PK CRF page.
    Time FrameWeeks 12 & 24: pre-dose (0hr), 2hr & 4hr post-dose

    Outcome Measure Data

    Analysis Population Description
    The PK analysis set consisted of all patients from FAS who had evaluable PK data.
    Arm/Group TitleDeferasirox
    Arm/Group DescriptionAll patients were treated with 10mg/kg/day deferasirox with dose adjustments after 4 weeks of treatment according to baseline Liver Iron Concentration (LIC).
    Measure Participants22
    4 weeks: 0hr pre-dose
    6.513
    (75.891)
    4 weeks: 2hr post-dose
    48.556
    (58.006)
    4 weeks: 4hr post-dose
    44.652
    (69.392)

    Adverse Events

    Time FrameAdverse events and serious adverse events were collected for the maximum actual duration of treatment exposure and follow up for a participant per the protocol for approximately 63.2 months.
    Adverse Event Reporting Description All cause mortality (deaths) was collected for as long as participants could be contacted from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV) up to a maximum of 7 years.
    Arm/Group TitleChineseNon-ChineseAll Patients
    Arm/Group DescriptionThis group was comprised of Chinese participants onlyThis group was comprised of non- Chinese participants onlyThis group was comprised of all patients: Chinese and non-Chinese participants
    All Cause Mortality
    ChineseNon-ChineseAll Patients
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/68 (2.9%) 0/66 (0%) 2/134 (1.5%)
    Serious Adverse Events
    ChineseNon-ChineseAll Patients
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total15/68 (22.1%) 30/66 (45.5%) 45/134 (33.6%)
    Blood and lymphatic system disorders
    Anaemia2/68 (2.9%) 4/66 (6.1%) 6/134 (4.5%)
    Extramedullary haemopoiesis0/68 (0%) 2/66 (3%) 2/134 (1.5%)
    Haemolysis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Haemolytic anaemia1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Hypersplenism2/68 (2.9%) 0/66 (0%) 2/134 (1.5%)
    Splenomegaly2/68 (2.9%) 0/66 (0%) 2/134 (1.5%)
    Thrombocytosis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Cardiac disorders
    Atrial fibrillation0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Cardiac failure2/68 (2.9%) 0/66 (0%) 2/134 (1.5%)
    Sinus tachycardia1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Eye disorders
    Cataract0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Gastrointestinal disorders
    Abdominal pain0/68 (0%) 2/66 (3%) 2/134 (1.5%)
    Abdominal pain upper0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Diarrhoea0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Enteritis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Inguinal hernia1/68 (1.5%) 1/66 (1.5%) 2/134 (1.5%)
    Pancreatitis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Peptic ulcer0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Superior mesenteric artery syndrome0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    General disorders
    Fatigue0/68 (0%) 2/66 (3%) 2/134 (1.5%)
    Generalised oedema0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Malaise0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Pyrexia0/68 (0%) 3/66 (4.5%) 3/134 (2.2%)
    Hepatobiliary disorders
    Biliary colic0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Cholecystitis1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Cholecystitis acute0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Cholelithiasis1/68 (1.5%) 3/66 (4.5%) 4/134 (3%)
    Hepatic fibrosis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Jaundice1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Infections and infestations
    Bronchitis1/68 (1.5%) 1/66 (1.5%) 2/134 (1.5%)
    Epididymitis1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Gastroenteritis0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Lung infection1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Pharyngitis0/68 (0%) 2/66 (3%) 2/134 (1.5%)
    Pharyngotonsillitis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Pneumonia3/68 (4.4%) 4/66 (6.1%) 7/134 (5.2%)
    Pyelonephritis acute0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Sepsis1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Tonsillitis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Upper respiratory tract infection0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Urinary tract infection0/68 (0%) 3/66 (4.5%) 3/134 (2.2%)
    Varicella0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Injury, poisoning and procedural complications
    Compression fracture0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Fracture0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Limb injury0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Skin laceration0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Spinal compression fracture0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Spinal fracture0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Upper limb fracture0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Metabolism and nutrition disorders
    Hyperglycaemic hyperosmolar nonketotic syndrome0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Type 2 diabetes mellitus1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Musculoskeletal and connective tissue disorders
    Osteoporosis1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Spinal osteoarthritis1/68 (1.5%) 0/66 (0%) 1/134 (0.7%)
    Tendonitis0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Hepatocellular carcinoma0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Nervous system disorders
    Cerebrovascular accident0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Dizziness0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Respiratory, thoracic and mediastinal disorders
    Bronchospasm0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Dyspnoea0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Pulmonary hypertension0/68 (0%) 1/66 (1.5%) 1/134 (0.7%)
    Other (Not Including Serious) Adverse Events
    ChineseNon-ChineseAll Patients
    Affected / at Risk (%)# EventsAffected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total26/68 (38.2%) 58/66 (87.9%) 84/134 (62.7%)
    Blood and lymphatic system disorders
    Anaemia0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Gastrointestinal disorders
    Abdominal discomfort2/68 (2.9%) 5/66 (7.6%) 7/134 (5.2%)
    Abdominal pain0/68 (0%) 15/66 (22.7%) 15/134 (11.2%)
    Abdominal pain upper0/68 (0%) 9/66 (13.6%) 9/134 (6.7%)
    Constipation0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Dental caries0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Diarrhoea1/68 (1.5%) 19/66 (28.8%) 20/134 (14.9%)
    Dyspepsia0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Gastritis0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Nausea2/68 (2.9%) 10/66 (15.2%) 12/134 (9%)
    Toothache0/68 (0%) 7/66 (10.6%) 7/134 (5.2%)
    Vomiting1/68 (1.5%) 11/66 (16.7%) 12/134 (9%)
    General disorders
    Fatigue1/68 (1.5%) 12/66 (18.2%) 13/134 (9.7%)
    Influenza like illness0/68 (0%) 7/66 (10.6%) 7/134 (5.2%)
    Pyrexia3/68 (4.4%) 14/66 (21.2%) 17/134 (12.7%)
    Hepatobiliary disorders
    Cholelithiasis1/68 (1.5%) 6/66 (9.1%) 7/134 (5.2%)
    Infections and infestations
    Conjunctivitis0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Gastroenteritis1/68 (1.5%) 9/66 (13.6%) 10/134 (7.5%)
    Influenza0/68 (0%) 11/66 (16.7%) 11/134 (8.2%)
    Pharyngitis0/68 (0%) 11/66 (16.7%) 11/134 (8.2%)
    Tonsillitis0/68 (0%) 12/66 (18.2%) 12/134 (9%)
    Upper respiratory tract infection7/68 (10.3%) 27/66 (40.9%) 34/134 (25.4%)
    Urinary tract infection2/68 (2.9%) 8/66 (12.1%) 10/134 (7.5%)
    Investigations
    Blood creatinine increased1/68 (1.5%) 4/66 (6.1%) 5/134 (3.7%)
    Platelet count increased13/68 (19.1%) 1/66 (1.5%) 14/134 (10.4%)
    Urine protein/creatinine ratio increased0/68 (0%) 6/66 (9.1%) 6/134 (4.5%)
    Metabolism and nutrition disorders
    Hyperphosphataemia0/68 (0%) 8/66 (12.1%) 8/134 (6%)
    Hyperuricaemia1/68 (1.5%) 5/66 (7.6%) 6/134 (4.5%)
    Vitamin D deficiency0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Musculoskeletal and connective tissue disorders
    Arthralgia0/68 (0%) 8/66 (12.1%) 8/134 (6%)
    Back pain0/68 (0%) 16/66 (24.2%) 16/134 (11.9%)
    Flank pain0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Myalgia0/68 (0%) 10/66 (15.2%) 10/134 (7.5%)
    Osteoporosis1/68 (1.5%) 4/66 (6.1%) 5/134 (3.7%)
    Pain in extremity0/68 (0%) 6/66 (9.1%) 6/134 (4.5%)
    Nervous system disorders
    Dizziness0/68 (0%) 8/66 (12.1%) 8/134 (6%)
    Headache0/68 (0%) 27/66 (40.9%) 27/134 (20.1%)
    Psychiatric disorders
    Anxiety0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Insomnia0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Renal and urinary disorders
    Dysuria0/68 (0%) 4/66 (6.1%) 4/134 (3%)
    Respiratory, thoracic and mediastinal disorders
    Cough0/68 (0%) 8/66 (12.1%) 8/134 (6%)
    Dyspnoea0/68 (0%) 6/66 (9.1%) 6/134 (4.5%)
    Nasal congestion0/68 (0%) 11/66 (16.7%) 11/134 (8.2%)
    Oropharyngeal pain0/68 (0%) 16/66 (24.2%) 16/134 (11.9%)
    Productive cough0/68 (0%) 8/66 (12.1%) 8/134 (6%)
    Pulmonary hypertension0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)
    Rhinorrhoea0/68 (0%) 5/66 (7.6%) 5/134 (3.7%)

    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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.

    Results Point of Contact

    Name/TitleStudy Director
    OrganizationNovartis Pharmaceuticals
    Phone862-778-8300
    Emailnovartis.email@novartis.com
    Responsible Party:
    Novartis Pharmaceuticals
    ClinicalTrials.gov Identifier:
    NCT01709838
    Other Study ID Numbers:
    • CICL670E2419
    • 2012-000650-64
    First Posted:
    Oct 18, 2012
    Last Update Posted:
    Oct 2, 2019
    Last Verified:
    Sep 1, 2019