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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01709838
Recruitment Status : Completed
First Posted : October 18, 2012
Results First Posted : August 28, 2019
Last Update Posted : October 2, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

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 disease Intervention/treatment Phase
Non-transfusion Dependent Thalassemia Drug: deferasirox Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 134 participants
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 : December 6, 2012
Actual Primary Completion Date : January 3, 2015
Actual Study Completion Date : January 17, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Iron Thalassemia
Drug Information available for: Deferasirox

Arm Intervention/treatment
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 Name: ICL670




Primary Outcome Measures :
  1. Absolute Change in Liver Iron Content (LIC) at 52 Weeks From Baseline [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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™) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline, 52 weeks ]
    Absolute change in serum ferritin from baseline after 52 weeks of treatment

  11. PK Parameters: AUCtau [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.



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Ages Eligible for Study:   10 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01709838


Locations
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China, Guangxi
Novartis Investigative Site
Nanning, Guangxi, China, 530021
Greece
Novartis Investigative Site
Goudi-Athens, GR, Greece, 115 27
Italy
Novartis Investigative Site
Cagliari, CA, Italy, 09121
Novartis Investigative Site
Milano, MI, Italy, 20122
Lebanon
Novartis Investigative Site
Hazmiyeh, Beirut, Lebanon, PO BOX 213
Thailand
Novartis Investigative Site
Bangkok, Thailand, 10700
Tunisia
Novartis Investigative Site
Tunis, Tunisia, 1006
Turkey
Novartis Investigative Site
Adana, Turkey, 01330
Novartis Investigative Site
Istanbul, Turkey, 34093
Novartis Investigative Site
Izmir, Turkey, 35040
United Kingdom
Novartis Investigative Site
London, United Kingdom, NW1 2PJ
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  Study Documents (Full-Text)

Documents provided by Novartis ( Novartis Pharmaceuticals ):
Statistical Analysis Plan  [PDF] January 23, 2019
Study Protocol  [PDF] September 4, 2014


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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01709838    
Other Study ID Numbers: CICL670E2419
2012-000650-64 ( EudraCT Number )
First Posted: October 18, 2012    Key Record Dates
Results First Posted: August 28, 2019
Last Update Posted: October 2, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent expert panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data is currently available according to the process described on www.clinicalstudydatarequest.com.

URL: https://www.clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Non-transfusion dependent thalassemia
NTDT
deferasirox
ICL670
LIC
Liver Iron Concentration
Additional relevant MeSH terms:
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Thalassemia
Anemia, Hemolytic, Congenital
Anemia, Hemolytic
Anemia
Hematologic Diseases
Hemoglobinopathies
Genetic Diseases, Inborn
Deferasirox
Iron Chelating Agents
Chelating Agents
Sequestering Agents
Molecular Mechanisms of Pharmacological Action