Efficacy and Safety of Deferasirox in Non-transfusion Dependent Thalassemia Patients With Iron Overload (THALASSA)
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Thalassemia Intermedia Syndrome |
Drug: deferasirox Drug: Placebo |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| 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 |
- Change in Liver Iron Content (LIC) From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]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.
- Change in Liver Iron Content (LIC) From Baseline to Week 24 [ Time Frame: Baseline, Week 24 ] [ Designated as safety issue: No ]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.
- Change in Serum Ferritin Between Baseline and Fourth Quarter [ Time Frame: Baseline, (Day 286 to End of Study [Day 365]) ] [ Designated as safety issue: No ]
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. The estimates for the 4th quarter were obtained from a repeated measurements model with quarter as covariate, treatment as factor, and a treatment*quarter interaction.
- Change in Serum Ferritin Between Baseline and Second Quarter [ Time Frame: Baseline, (Day 106 to Day 195) ] [ Designated as safety issue: No ]
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. The estimates for the 2nd quarter were obtained from a repeated measurements model with quarter as covariate, treatment as factor, and a treatment*quarter interaction.
- Percentage of Participants With Adverse Events Graded Mild, Moderate and Severe [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]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.
- Change in Liver Iron Content (LIC) From Baseline At Week 24 and Week 52 in Patients With Dose Increases After Week 24 [ Time Frame: Baseline, Week 24, Week 52 ] [ Designated as safety issue: No ]LIC was measured by magnetic resonance imaging technique at baseline, Week 24 and Week 52. Dose Doubling (Dose Increases) began at Week 24.
- Correlation Between Serum Ferritin and LIC (Liver Iron Content) [ Time Frame: Baseline, 52 weeks ] [ Designated as safety issue: No ]
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.
- Change From Baseline in Hemoglobin at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]Blood was collected for Hemoglobin at baseline and Month 12. Change from baseline= Month 12 hemoglobin - baseline hemoglobin.
- Change From Baseline in Transferrin Saturation at Month 12 [ Time Frame: Baseline, Month 12 ] [ Designated as safety issue: No ]Blood was collected for transferrin saturation at Baseline and Month 12. Change from baseline= Month 12 transferrin saturation - baseline transferrin saturation.
- Change in Liver Iron Content (LIC) in Placebo Patients From Baseline to Week 52 [ Time Frame: Baseline, Week 52 ] [ Designated as safety issue: No ]LIC was measured by magnetic resonance imaging technique at baseline and Week 52. The change in liver iron content for participants in the placebo arm was used to assess the iron accumulation rate.
- Percentage of Participants With Notable Abnormal Post-baseline Laboratory Results [ Time Frame: 52 Weeks ] [ Designated as safety issue: No ]
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)
- Percentage of Participants With Notably Abnormal Post-baseline Systolic Blood Pressure [ Time Frame: Baseline, 52 Weeks ] [ Designated as safety issue: No ]
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
- Percentage of Participants With Notably Abnormal Post-baseline Diastolic Blood Pressure [ Time Frame: Baseline, 52 Weeks ] [ Designated as safety issue: No ]
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
- Percentage of Participants With Notably Abnormal Post-baseline Pulse Rate [ Time Frame: Baseline, 52 Weeks ] [ Designated as safety issue: No ]
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
| Enrollment: | 166 |
| Study Start Date: | November 2008 |
| Study Completion Date: | June 2011 |
| Primary Completion Date: | June 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: 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 Content (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Drug: deferasirox
Supplied as 125 mg, 250 mg and 500 mg tablets.
|
|
Experimental: 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 Content (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Drug: deferasirox
Supplied as 125 mg, 250 mg and 500 mg tablets.
|
|
Placebo Comparator: 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 Content (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Drug: Placebo
Supplied as matching 125 mg, 250 mg and 500 mg tablets.
|
|
Placebo Comparator: 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 Content (LIC) was assessed. Based on the LIC and change from baseline in LIC participants were eligible for dose escalation.
|
Drug: Placebo
Supplied as matching 125 mg, 250 mg and 500 mg tablets.
|
Eligibility| Ages Eligible for Study: | 10 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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 content ≥ 5 mg/g dry weight measured by Magnetic resonance imaging (MRI) before study start
- Serum ferritin >300 ng/mL at screening
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
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations| United States, California | |
| Children's Hospital & Research Center Oakland | |
| Oakland, California, United States, 94609-1809 | |
| United States, Illinois | |
| Children's Memorial Hospital/Division of Hematology/Oncology | |
| Chicago, Illinois, United States, 60614-3394 | |
| United States, New York | |
| New York Presbyterian Hospital/Weill Medical College of Cornell University | |
| New York, New York, United States, 10021 | |
| Greece | |
| Novartis Investigative Site | |
| Athens, Greece | |
| Novartis Investigative Site | |
| Patras, Greece | |
| Novartis Investigative Site | |
| Thessaloniki, Greece | |
| Italy | |
| Novartis Investigative Site | |
| Cagliari, Italy | |
| Novartis Investigative Site | |
| Genova, Italy | |
| Novartis Investigative Site | |
| Milano, Italy | |
| Novartis Investigative Site | |
| Napoli, Italy | |
| Novartis Investigative Site | |
| Rome, Italy | |
| Lebanon | |
| Novartis Investigative Site | |
| Beirut, Lebanon | |
| Malaysia | |
| Novartis Investigative Site | |
| Ampang Selangor, Malaysia | |
| Novartis Investigative Site | |
| Kuala Lumpur, Malaysia | |
| Taiwan | |
| Novartis Investigative Site | |
| Taipei, Taiwan | |
| Thailand | |
| Novartis Investigative Site | |
| Bangkok, Thailand | |
| Turkey | |
| Novartis Investigative Site | |
| Adana, Turkey | |
| Novartis Investigative Site | |
| Ankara, Turkey | |
| Novartis Investigative Site | |
| Istanbul, Turkey | |
| Novartis Investigative Site | |
| Izmir, Turkey | |
| United Kingdom | |
| Novartis Investigative Site | |
| London, United Kingdom | |
| Study Director: | Novartis Pharmaceuticals | Novartis Pharmaceuticals |
More Information
Additional Information:
No publications provided
| Responsible Party: | Novartis ( Novartis Pharmaceuticals ) |
| ClinicalTrials.gov Identifier: | NCT00873041 History of Changes |
| Obsolete Identifiers: | NCT01185106 |
| Other Study ID Numbers: | CICL670A2209, EudraCT 2007-007000-15 |
| Study First Received: | March 30, 2009 |
| Results First Received: | June 20, 2012 |
| Last Updated: | August 22, 2012 |
| Health Authority: | United States: Food and Drug Administration European Union: European Medicine Agency Greece: Ministry of Health and Welfare Italy: The Italian Medicines Agency Lebanon: Institutional Review Board Taiwan: Health Authority Malaysia: Ministry of Health Thailand: Ministry of Public Health Turkey: Ministry of Health United Kingdom: Medicines and Healthcare Products Regulatory Agency |
Keywords provided by Novartis:
|
Thalassemia thalassemia intermedia alpha-thalassemia beta-thalassemia |
deferasirox iron overload non-transfusion dependent |
Additional relevant MeSH terms:
|
Beta-Thalassemia Thalassemia Iron Overload Anemia, Hemolytic, Congenital Anemia, Hemolytic Anemia Hematologic Diseases Hemoglobinopathies Genetic Diseases, Inborn Iron Metabolism Disorders Metabolic Diseases |
Iron Deferasirox Trace Elements Micronutrients Growth Substances Physiological Effects of Drugs Pharmacologic Actions Iron Chelating Agents Chelating Agents Molecular Mechanisms of Pharmacological Action |
ClinicalTrials.gov processed this record on May 19, 2013