An Open Label, Multi-center, Efficacy and Safety Study of Deferasirox in Iron Overloaded Patients With Non-transfusion Dependent Thalassemia. (MACS1935)

This study is currently recruiting participants.
Verified February 2014 by Novartis
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier:
NCT01709838
First received: October 16, 2012
Last updated: February 25, 2014
Last verified: February 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) over 260 weeks.


Condition Intervention Phase
Non-transfusion Dependent Thalassemia
Drug: ICL670 deferasirox
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
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 (MRI) from baseline after 52 weeks of treatment


Secondary Outcome Measures:
  • Medical Outcomes Study Short Form-36 [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    Absolute change from baseline to 52 weeks. The SF-36 is a self-administered questionnaire for adults (> 18 years of age) and contains 36 items which measure: Physical functioning, Role limitation due to physical health problems, Bodily pain, Role limitations due to emotional problems, General mental health and Health change over the past year.

  • Pediatric Quality of Life Questionnaires [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    The PedsOL is a modular approach to measuring health-related quality of life in pediatrics (>10 but </= 18 years of age). 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, 24 weeks ] [ Designated as safety issue: No ]
    Absolute change in liver iron concentration (MRI) from baseline after 24 weeks of treatment

  • serum ferritin vs liver iron concentration [ Time Frame: baseline, week 24 and week 52 ] [ Designated as safety issue: No ]
    baseline, week 24, week 52 serum ferritin versus baseline, week 24, week 52 liver iron concentration

  • change in serum ferritin [ Time Frame: baseline, 52 weeks ] [ Designated as safety issue: No ]
    Absolute change in serum ferritin from baseline after 52 weeks of treatment

  • endocrine laboratory parameters [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]
    Absolute change from baseline 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: 52 weeks ] [ Designated as safety issue: No ]
    PAS will be used in all pharmacokinetic data analysis and PK summary statistics. Th Pk parameters, AUCtau, Cmas 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: 52 weeks ] [ Designated as safety issue: Yes ]
    number of participants with adverse events as a measure of safety and tolerability

  • Change in liver iron concentration [ Time Frame: every 4 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 4 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


Estimated Enrollment: 120
Study Start Date: December 2012
Estimated Study Completion Date: January 2020
Estimated Primary Completion Date: January 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Deferasirox
one arm, deferasirox, LIC based dose titration
Drug: ICL670 deferasirox
deferasirox

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 24 and 52 . 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 according to genotype, 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 ALT >5 x ULN active hepatitis B or C cirrhosis

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

Contacts
Contact: Novartis Pharmaceuticals +41613241111
Contact: Novartis Pharmaceuticals

Locations
China, Guangxi
Novartis Investigative Site Active, not recruiting
Nanning, Guangxi, China, 530021
Greece
Novartis Investigative Site Active, not recruiting
Athens, Greece, GR-115 27
Italy
Novartis Investigative Site Active, not recruiting
Cagliari, CA, Italy, 09121
Novartis Investigative Site Active, not recruiting
Milano, MI, Italy, 20122
Lebanon
Novartis Investigative Site Recruiting
Hazmiyeh, Lebanon
Russian Federation
Novartis Investigative Site Not yet recruiting
Moskow, Russia, Russian Federation, 117198
Thailand
Novartis Investigative Site Active, not recruiting
Bangkok, Thailand, 10700
Tunisia
Novartis Investigative Site Active, not recruiting
Tunis, Tunisia, 1006
Turkey
Novartis Investigative Site Active, not recruiting
Adana, Turkey, 01330
Novartis Investigative Site Active, not recruiting
Istanbul, Turkey, 34093
Novartis Investigative Site Active, not recruiting
Izmir, Turkey, 35040
United Kingdom
Novartis Investigative Site Recruiting
Leicester, United Kingdom, LE1 5WW
Novartis Investigative Site Recruiting
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: February 25, 2014
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
Thailand: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on April 14, 2014