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Non-transfusion Dependent ThalassemiaPhase 2THALASSANCT00873041

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

A Phase 2 study testing deferasirox in people with Non-transfusion Dependent Thalassemia, run by Novartis Pharmaceuticals at 21 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 10 years and older
Conditions the study is for
Non-transfusion Dependent Thalassemia
What is being tested?
deferasirox
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
166 participants
Where
21 sitesin 9 countries
Study dates
Nov 2008to Jun 2012
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 10 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Core Inclusion Criteria:

  • Male or female aged ≥ 10 years with non-transfusion dependent syndromes, not requiring transfusion within 6 months prior to study start. Note: there was a local country amendment for Greece only to change the age specific inclusion criteria to ≥ 18 years old
  • Liver iron concentration ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
  • Serum ferritin >300 ng/mL at screening

Core 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

Extension Inclusion Criteria:

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

Extension Exclusion Criteria:

  • 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.)

Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

21 sites in 9 countries.

21 sites in 9 countries

Italy5 sites
  • Novartis Investigative Site

    Cagliari

  • Novartis Investigative Site

    Genova

  • Novartis Investigative Site

    Milan

  • Novartis Investigative Site

    Naples

  • Novartis Investigative Site

    Rome

Other trials in Italy

Turkey (Türkiye)4 sites
  • Novartis Investigative Site

    Adana

  • Novartis Investigative Site

    Ankara

  • Novartis Investigative Site

    Istanbul

  • Novartis Investigative Site

    Izmir

Other trials in Turkey (Türkiye)

United States3 sites
  • Children's Memorial Hospital/Division of Hematology/Oncology

    Chicago, Illinois, 60614-3394

  • New York Presbyterian Hospital/Weill Medical College of Cornell University

    New York, New York, 10021

  • Children's Hospital & Research Center Oakland

    Oakland, California, 94609-1809

Other trials in United States

Greece3 sites
  • Novartis Investigative Site

    Athens

  • Novartis Investigative Site

    Pátrai

  • Novartis Investigative Site

    Thessaloniki

Other trials in Greece

Malaysia2 sites
  • Novartis Investigative Site

    Ampang Selangor

  • Novartis Investigative Site

    Kuala Lumpur

Other trials in Malaysia

Lebanon1 site
  • Novartis Investigative Site

    Beirut

Other trials in Lebanon

Taiwan1 site
  • Novartis Investigative Site

    Taipei

Other trials in Taiwan

Thailand1 site
  • Novartis Investigative Site

    Bangkok

Other trials in Thailand

United Kingdom1 site
  • Novartis Investigative Site

    London

Other trials in United Kingdom

About this study

Official title: 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

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).

Being tested
deferasirox, placebo
Keywords
Thalassemia, thalassemia intermedia, alpha-thalassemia, beta-thalassemia, deferasirox, iron overload, non-transfusion dependent
Medical subject headings
Thalassemia, beta-Thalassemia, alpha-Thalassemia, Iron Overload

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • deferasiroxDrug

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

  • placeboDrug

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

Study groups in NCT00873041
Study groupRoleWhat they receive
5 mg/kg/day deferasiroxExperimentalParticipants 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.
Receives: Drug: deferasirox; Drug: placebo
10 mg/kg/day deferasiroxExperimentalParticipants 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.
Receives: Drug: deferasirox; Drug: placebo
5 mg/kg/day placeboPlacebo comparatorPlacebo 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.
Receives: Drug: placebo
10 mg/kg/day placeboPlacebo comparatorPlacebo 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.
Receives: Drug: placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, Week 52

  2. 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.

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

Secondary outcomes (18)
  1. Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 24

    LIC was measured by magnetic resonance imaging technique at baseline and Week 24. Estimates were obtained from an Analysis of Covariance (ANCOVA) model for change in LIC between baseline and Week 24 with treatment as factor and baseline LIC as covariate.

    Measured: Baseline, Week 24

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

    Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug.

    Fourth quarter serum ferritin average was the average of all serum ferritin values obtained within days 286- End of Study.

    Change from baseline: fourth quarter serum ferritin average - baseline serum ferritin average.

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

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

    Baseline serum ferritin average was the average of all available ferritin values from screening to last sample prior to the first intake of study drug.

    Second quarter serum ferritin average was the average of all serum ferritin values obtained within days 106-195.

    Change from baseline: second quarter serum ferritin average - baseline serum ferritin average.

    Measured: Baseline, (Day 106 to Day 195)

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

    Percentage of Participants with Mild, Moderate and Severe adverse events (AE) any primary system organ class regardless of study drug relationship. A patient with multiple occurrences of an AE is counted only once in the AE category for that treatment. A patient with multiple severity ratings for an AE while on a treatment is only counted once under the maximum rating.

    Measured: 52 Weeks

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

    LIC was measured by magnetic resonance imaging technique at baseline, Week 24 and Week 52. Dose Doubling (Dose Increases) began at Week 24.

    Measured: Baseline, Week 24, Week 52

  6. Core Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)

    The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for the following cases:

    • Baseline serum ferritin versus baseline LIC
    • Serum ferritin difference from baseline at fourth quarter versus difference from baseline in LIC at Week 52.

    A value of 1.0 indicates a perfect correlation.

    Measured: Baseline, 52 weeks

  7. Core Study: Change From Baseline in Hemoglobin at Month 12

    Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin.

    Measured: Baseline, Month 12

  8. Core Study: Change From Baseline in Transferrin Saturation at Month 12

    Blood was collected for transferrin saturation at Baseline and Month 12. Change from baseline= Month 12 transferrin saturation - baseline transferrin saturation.

    Measured: Baseline, Month 12

  9. Core Study: Change in Liver Iron Concentration (LIC) in Placebo Patients From Baseline to Week 52

    LIC was measured by magnetic resonance imaging technique at baseline and Week 52. The change in liver iron concentration for participants in the placebo arm was used to assess the iron accumulation rate.

    Measured: Baseline, Week 52

  10. Core Study: Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results

    The percentage of participants with notable laboratory results:

    Platelet count: (<100 x 10^9/L)

    Absolute neutrophils: (<1.5 x 10^9/L)

    Alanine aminotransferase (ALT): (>5 x Upper limit normal (ULN) and >2 x baseline).

    Aspartate aminotransferase (AST): (>5 x ULN and >2 x baseline)

    Serum creatinine: (>33% increase from baseline and >ULN at ≥2 consecutive post-baseline values) Creatinine clearance: (<60 mL/min at ≥2 consecutive post-baseline values)

    Urinary protein/creatinine ratio: (≥ 1.0 mg/mg at ≥2 consecutive post-baseline values)

    Measured: 52 Weeks

  11. Core Study: Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure

    Systolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes.

    A Notably Abnormal Systolic Blood Pressure was defined as a measurement in one of the following two categories:

    High: ≥180 with an increase from baseline ≥20 mmHg

    Low: ≤90 with a decrease from baseline ≥20 mmHg

    Measured: Baseline, 52 Weeks

  12. Core Study: Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure

    Diastolic blood pressure was measured at each visit after the patient rested in the sitting position for at least 3 minutes.

    A Notably Abnormal Diastolic Blood Pressure was defined as a measurement in one of the following two categories:

    High: ≥105 with an increase from baseline ≥15 mmHg

    Low: ≤50 with a decrease from baseline ≥15 mmHg

    Measured: Baseline, 52 Weeks

  13. Core Study: Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate

    Pulse Rate was measured at each visit.

    A Notably Abnormal Pulse Rate was defined as a measurement in one of the following two categories:

    High: ≥120 with an increase from baseline ≥15 beats per minute (bpm)

    Low: ≤50 with a decrease from baseline ≥15 bpm

    Measured: Baseline, 52 Weeks

  14. Extension Study: Absolute Change in Serum Ferritin From Baseline to Eighth Quarter

    Blood was collected for serum ferritin at Core Baseline and monthly during the Eighth quarter of the Extension Study. Absolute change from Baseline: quarterly average - baseline average. A negative change from baseline indicated improvement.

    Measured: Core Baseline, Eighth Quarter (last 3 months of the study)

  15. Extension Study: Change in Liver Iron Concentration (LIC) From Baseline at Month 24

    LIC was measured by magnetic resonance imaging technique at Baseline and Month 24. A negative change from baseline indicated improvement.

    Measured: Core Baseline, Month 24

  16. Extension Study: Correlation Between Serum Ferritin and LIC (Liver Iron Concentration)

    The correlation between serum ferritin and LIC was investigated using a scatter plot with a regression line for serum ferritin difference from Baseline at Month 24 versus LIC difference from Baseline at Month 24.

    A value of 1.0 indicates a perfect correlation.

    Measured: Core Baseline, Month 24

  17. Extension Study: Change From Baseline in Hemoglobin at Month 24

    Blood was collected for Hemoglobin at Baseline and Month 24. Change from Baseline= Month 24 hemoglobin - Baseline hemoglobin.

    Measured: Core Baseline, Month 24

  18. Extension Study: Change From Baseline in Transferrin Saturation at Month 24

    Blood was collected for transferrin saturation at Baseline and Month 24. Change from baseline= Month 24 transferrin saturation - baseline transferrin saturation.

    Measured: Core Baseline, Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Apr 2009 (estimated)
  2. Study startNov 2008
  3. Primary completionJun 2011
  4. Study completionJun 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
166 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00873041
Sponsor's protocol ID
CICL670A2209
Other IDs
EudraCT 2007-007000-15
Acronym
THALASSA
Status last verified
May 2013
First submitted
30 Mar 2009
Last updated
9 Jul 2013

Publications

  • 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.

    PubMed 25212456
  • 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.

    PubMed 23553596

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing deferasirox in people with Non-transfusion Dependent Thalassemia, run by Novartis Pharmaceuticals at 21 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 9 Jul 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 21 sites in Italy, Turkey (Türkiye), United States, Greece, Malaysia and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 25 Sep 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Core Study: Change in Liver Iron Concentration (LIC) From Baseline to Week 52 (time frame: Baseline, Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00873041, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jul 2013.

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