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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01709838
First received: October 16, 2012
Last updated: November 18, 2014
Last verified: November 2014
  Purpose

To assess 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. To provide 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 Intervention Phase
Non-transfusion Dependent Thalassemia
Drug: ICL670 deferasirox
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Change in liver iron concentration [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    Absolute change in liver iron concentration measured by MRI from baseline after 52 weeks of treatment


Secondary Outcome Measures:
  • Medical Outcomes Study Short Form-36 [ Time Frame: baseline, up to 156 weeks ] [ Designated as safety issue: No ]
    Absolute change from baseline at 52, 104 and 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 perseptions, Vitality, Social functioning, Role limitations due to emotional problems, General mental health and Health change over the past year.

  • Pediatric Quality of Life Questionnaires [ Time Frame: baseline, up to 156 weeks ] [ Designated as safety issue: No ]
    Absolute change from baseline at 52, 104 and 156 weeks. The PedsOL is a modular approach to measuring health-related quality of life in children and adolescents (13 to 18 years). The approach includes both a child self-report and a parent proxy-report. The 23-item PedsQL Generic Core Scales encompass the essential core domains for pediatric health related quality of life measurement: physical functioning, emotional functioning, social functioning and school functioning.

  • Change in liver iron concentration [ Time Frame: baseline, up to 260 weeks ] [ Designated as safety issue: No ]
    Absolute change in liver iron concentration measured by MRI from baseline up to 260 weeks(approximately every 6 months)

  • Correlation between serum ferritin and liver iron concentration [ Time Frame: baseline, up to 260 weeks ] [ Designated as safety issue: No ]
    Change in ferritin vs change in liver iron concentration from baseline up to 260 weeks

  • Change in serum ferritin [ Time Frame: baseline, up to 260 weeks ] [ Designated as safety issue: No ]
    Absolute change in serum ferritin from baseline over time up to 260 weeks

  • Endocrine function laboratory parameters [ Time Frame: baseline, up to 260 weeks ] [ Designated as safety issue: No ]
    Absolute change over time from baseline up to 260 weeks in total and free testosterone (males), LH and FSH (females), TSH, total and free T4, total and free T3, fasting plasma glucose, insulin, insulin resistance and cortisol.

  • PK parameters [ Time Frame: up to 24 weeks ] [ Designated as safety issue: No ]
    A subset of patients (Pharmacokinetic Analysis Set) will be used in all pharmacokinetic data analysis and PK summary statistics. The PK parameters, AUCtau, Cmax and tmax may be determined using non-compartmental methods for deferasirox and its iron complex. Biofluid concentrations will be expressed in mass per volume units.

  • Adverse events [ Time Frame: up to 260 weeks ] [ Designated as safety issue: Yes ]
    The incidence of treatment-emergent Adverse Events (AEs) will be summarized. Deaths (reportable as SAEs) and non-fatal SAEs will be listed. Significant changes in laboratory values, ECG parameters, vital signs, ocular and auditory examinations after start of study will be documented as AEs.

  • Change in liver iron concentration [ Time Frame: every 24 weeks following baseline to week 260 ] [ Designated as safety issue: No ]
    Response rate in patients with baseline LIC >15 mg Fe/g dw defined as proportion of patients achieving LIC <5mg Fe/g dw and time to achieving LIC <5mg Fe/g dw.

  • Change in liver iron concentration [ Time Frame: every 24 weeks from week 52 to week 260 ] [ Designated as safety issue: Yes ]
    Long term efficacy and safety of treatment to target LIC of 3mg Fe/g dw followed by one or more treatment holidays until the LIC is ≥5 mg Fe/g dw.

  • Change in liver iron concentration [ Time Frame: every 24 weeks, from baseline to week 260 ] [ Designated as safety issue: No ]
    Absolute change from baseline LIC over time by non-transfusion dependent thalassemia (NTDT) syndrome


Enrollment: 134
Study Start Date: December 2012
Estimated Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Deferasirox
one arm, deferasirox, LIC based dose titration
Drug: ICL670 deferasirox
deferasirox
Other Name: Exjade

Detailed Description:

To assess the efficacy of deferasirox in patients with non-transfusion dependent thalassemia based on change in liver iron concentration from baseline after 52 weeks. Also, to evaluate the impact of deferasirox on the quality of life for adults and pediatric patients; correlate changes in serum ferritin and LIC, evaluate efficacy changes in NTDT syndrome, evaluate higher doses of deferasirox, assess endocrine function and examine PK parameters.To also assess the efficacy of treatment in patients with very high LIC (>15 mg Fe/g dw) at baseline and those who need re-treatment after having reached the target LIC < 3 mg Fe/g dw during the study.

  Eligibility

Ages Eligible for Study:   10 Years and older
Genders Eligible for Study:   Both
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

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  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01709838

Locations
China, Guangxi
Novartis Investigative Site
Nanning, Guangxi, China, 530021
Greece
Novartis Investigative Site
Athens, GR, Greece, GR-115 27
Italy
Novartis Investigative Site
Cagliari, CA, Italy, 09121
Novartis Investigative Site
Milano, MI, Italy, 20122
Lebanon
Novartis Investigative Site
Hazmiyeh, Lebanon
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
Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01709838     History of Changes
Other Study ID Numbers: CICL670E2419, 2012-000650-64
Study First Received: October 16, 2012
Last Updated: November 18, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Thailand: Food and Drug Administration
China: Food and Drug Administration
Greece: National Organization of Medicines
Italy: National Institute of Health
Lebanon: Ministry of public Health MOPH Lebanon
Russia: Ministry of Health of the Russian Federation
Turkey: Ministry of Health
Tunisia: Ministry of Public Health

Keywords provided by Novartis:
Non-transfusion dependent thalassemia, NTDT

Additional relevant MeSH terms:
Thalassemia
Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Congenital
Genetic Diseases, Inborn
Hematologic Diseases
Hemoglobinopathies
Deferasirox
Chelating Agents
Iron Chelating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Sequestering Agents

ClinicalTrials.gov processed this record on November 25, 2014