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

NCT00873041 | Completed Phase 2 Results

• 2 other identifiers: CICL670A2209EudraCT 2007-007000-15
• Study Type: interventional
• Target: 166
• Locations: 9 countries
• Sites: 21

Brief Summary

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).

Conditions

Non-transfusion Dependent Thalassemia

Keywords

Thalassemia; thalassemia intermedia; alpha-thalassemia; beta-thalassemia; deferasirox; iron overload; non-transfusion dependent

Outcome Measures

Primary Outcomes (2)

• Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52

  LIC was measured by magnetic resonance imaging technique at baseline and Week 52. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 52 with treatment as factor and baseline LIC as covariate.

  Baseline, Week 52

• Extension Study: Percentage of Participants Reaching a Liver Iron Concentration (LIC) < 5 mg Fe/g dw From Core Baseline to End of Extension Study

  Liver iron concentration was measured at Core Baseline and at the end of the Extension Study. Magnetic Resonance Imaging (MRI) scans were analyzed at a central laboratory to determine the LIC value. The percentage of participants with LIC \< 5 mgFe/g dw (milligram iron/gram dry weight) change from Baseline at the end of the Extension Study is reported.

  Core Baseline to End of Extension Study (up to 24 months)

Secondary Outcomes (18)

• Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24

  Baseline, Week 24

• Core Study: Change in Serum Ferritin Between Baseline and Fourth Quarter

  Baseline, (Day 286 to End of Study [Day 365])

• Core Study: Change in Serum Ferritin Between Baseline and Second Quarter

  Baseline, (Day 106 to Day 195)

• Core Study: Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe

  52 Weeks

• Core Study: Change in Liver Iron Concentration (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24

  Baseline, Week 24, Week 52

Study Arms (4)

5 mg/kg/day deferasirox

EXPERIMENTAL

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.

Drug: deferasirox; Drug: placebo

10 mg/kg/day deferasirox

EXPERIMENTAL

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.

Drug: deferasirox; Drug: placebo

5 mg/kg/day placebo

PLACEBO COMPARATOR

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.

Drug: placebo

10 mg/kg/day placebo

PLACEBO COMPARATOR

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.

Drug: placebo

Interventions

deferasirox DRUG

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

10 mg/kg/day deferasirox; 5 mg/kg/day deferasirox

placebo DRUG

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

10 mg/kg/day deferasirox; 10 mg/kg/day placebo; 5 mg/kg/day deferasirox; 5 mg/kg/day placebo

Eligibility Criteria

• Age: 10 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (21)

Children's Hospital & Research Center Oakland

Oakland, California, 94609-1809, United States

Location

Children's Memorial Hospital/Division of Hematology/Oncology

Chicago, Illinois, 60614-3394, United States

Location

New York Presbyterian Hospital/Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Novartis Investigative Site

Athens, Greece

Location

Novartis Investigative Site

Pátrai, Greece

Location

Novartis Investigative Site

Thessaloniki, Greece

Location

Novartis Investigative Site

Cagliari, Italy

Location

Novartis Investigative Site

Genova, Italy

Location

Novartis Investigative Site

Milan, Italy

Location

Novartis Investigative Site

Napoli, Italy

Location

Novartis Investigative Site

Rome, Italy

Location

Novartis Investigative Site

Beirut, Lebanon

Location

Novartis Investigative Site

Ampang Selangor, Malaysia

Location

Novartis Investigative Site

Kuala Lumpur, Malaysia

Location

Novartis Investigative Site

Taipei, Taiwan

Location

Novartis Investigative Site

Bangkok, Thailand

Location

Novartis Investigative Site

Adana, Turkey (Türkiye)

Location

Novartis Investigative Site

Ankara, Turkey (Türkiye)

Location

Novartis Investigative Site

Istanbul, Turkey (Türkiye)

Location

Novartis Investigative Site

Izmir, Turkey (Türkiye)

Location

Novartis Investigative Site

London, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 25212456 DERIVED

• 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.

  PMID: 23553596 DERIVED

Related Links

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

MeSH Terms

Conditions

Thalassemia; beta-Thalassemia; alpha-Thalassemia; Iron Overload

Interventions

Deferasirox

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Iron Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Benzoates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2009
• First Posted: April 1, 2009
• Study Start: November 1, 2008
• Primary Completion: June 1, 2011
• Study Completion: June 1, 2012
• Last Updated: July 9, 2013
• Results First Posted: September 25, 2012

Record last verified: 2013-05

Locations

LE (1); MY (2); TH (1); IT (5); TU (4); GR (3); US (3); TW (1); GB (1)