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

NCT ID: NCT00873041

Last Updated: 2013-07-09

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

166 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-11-30

Study Completion Date

2012-06-30

Brief Summary

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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).

Detailed Description

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Conditions

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Non-transfusion Dependent Thalassemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

deferasirox

Intervention Type DRUG

Supplied as 125 mg, 250 mg and 500 mg tablets.

placebo

Intervention Type DRUG

Supplied as matching 125 mg, 250 mg and 500 mg tablets.

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.

Group Type EXPERIMENTAL

deferasirox

Intervention Type DRUG

Supplied as 125 mg, 250 mg and 500 mg tablets.

placebo

Intervention Type DRUG

Supplied as matching 125 mg, 250 mg and 500 mg tablets.

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Supplied as matching 125 mg, 250 mg and 500 mg tablets.

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.

Group Type PLACEBO_COMPARATOR

placebo

Intervention Type DRUG

Supplied as matching 125 mg, 250 mg and 500 mg tablets.

Interventions

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deferasirox

Supplied as 125 mg, 250 mg and 500 mg tablets.

Intervention Type DRUG

placebo

Supplied as matching 125 mg, 250 mg and 500 mg tablets.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
* Serum ferritin \>300 ng/mL at screening


* Patients who completed the core CICL670A2209 clinical trial
* Written informed consent obtained prior entry to one year extension study CICL670A2209

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


* 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.)
Minimum Eligible Age

10 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

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Children's Hospital & Research Center Oakland

Oakland, California, United States

Site Status

Children's Memorial Hospital/Division of Hematology/Oncology

Chicago, Illinois, United States

Site Status

New York Presbyterian Hospital/Weill Medical College of Cornell University

New York, New York, United States

Site Status

Novartis Investigative Site

Athens, , Greece

Site Status

Novartis Investigative Site

Pátrai, , Greece

Site Status

Novartis Investigative Site

Thessaloniki, , Greece

Site Status

Novartis Investigative Site

Cagliari, , Italy

Site Status

Novartis Investigative Site

Genova, , Italy

Site Status

Novartis Investigative Site

Milan, , Italy

Site Status

Novartis Investigative Site

Napoli, , Italy

Site Status

Novartis Investigative Site

Rome, , Italy

Site Status

Novartis Investigative Site

Beirut, , Lebanon

Site Status

Novartis Investigative Site

Ampang Selangor, , Malaysia

Site Status

Novartis Investigative Site

Kuala Lumpur, , Malaysia

Site Status

Novartis Investigative Site

Taipei, , Taiwan

Site Status

Novartis Investigative Site

Bangkok, , Thailand

Site Status

Novartis Investigative Site

Adana, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Ankara, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Istanbul, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

Izmir, , Turkey (Türkiye)

Site Status

Novartis Investigative Site

London, , United Kingdom

Site Status

Countries

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United States Greece Italy Lebanon Malaysia Taiwan Thailand Turkey (Türkiye) United Kingdom

References

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Taher AT, Porter JB, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, Siritanaratkul N, Origa R, Karakas Z, Habr D, Zhu Z, Cappellini MD. Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non-transfusion-dependent thalassaemia. Br J Haematol. 2015 Jan;168(2):284-90. doi: 10.1111/bjh.13119. Epub 2014 Sep 12.

Reference Type DERIVED
PMID: 25212456 (View on PubMed)

Taher AT, Porter JB, Viprakasit V, Kattamis A, Chuncharunee S, Sutcharitchan P, Siritanaratkul N, Galanello R, Karakas Z, Lawniczek T, Habr D, Ros J, Zhang Y, Cappellini MD. Deferasirox demonstrates a dose-dependent reduction in liver iron concentration and consistent efficacy across subgroups of non-transfusion-dependent thalassemia patients. Am J Hematol. 2013 Jun;88(6):503-6. doi: 10.1002/ajh.23445. Epub 2013 May 13.

Reference Type DERIVED
PMID: 23553596 (View on PubMed)

Related Links

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http://www.novartisclinicaltrials.com/etrials/searchTrial.do?trialID=717

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

Other Identifiers

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EudraCT 2007-007000-15

Identifier Type: REGISTRY

Identifier Source: secondary_id

CICL670A2209

Identifier Type: -

Identifier Source: org_study_id

NCT01185106

Identifier Type: -

Identifier Source: nct_alias

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