Anemia, Hemosiderosis
Conditions
Keywords
β-thalassemia, rare chronic anemia, iron overload, deferasirox, chronic anemias, transfusional hemosiderosis
Brief summary
A 1-year randomized Phase II core trial was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia and other rare chronic anemia 2 years of age and older. Patients who successfully completed the main trial may continue in the extension trial to receive chelation therapy with deferasirox for up to 3 years. Extension was prolonged to 4 years. The objective of this study is to assess the long-term safety and efficacy of deferasirox in these patient groups.
Interventions
DRUGDeferasirox
Deferasirox available as 125 mg, 250 mg or 500 mg tablets
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients completed the planned 12-month core study * Female patients who have reached menarche and who are sexually active must use double-barrier contraception, oral contraceptive plus barrier contraceptive, or must have undergone clinically documented total hysterectomy and/or ovariectomy, or tubal ligation * Written informed consent obtained from the patient and/or legal guardian on the patient's behalf in accordance with the national legislation
Exclusion criteria
* Pregnant or breast feeding patients Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Core study Baseline to the end of the study (up to 60 months) | Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study | Core study Baseline to end of extension study (up to 60 months) | Liver iron concentration was monitored at the start of the core study, the end of the core study, and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. |
| The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study | Core study Baseline to end of extension study (up to 60 months) | Liver iron concentration was monitored at the end of the core study and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. Pediatric participants or participants with a medical contraindication to liver biopsy were allowed the use of SQUID in the extension study. |
| The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | Core study Baseline to end of extension study (up to 60 months) | Serum ferritin was monitored monthly and the dose of deferasirox was increased or decreased in steps of 5 to 10 mg/kg/day up to a maximum of 40 mg/kg/day if appropriate, every 3 months. If serum ferritin fell to 500 ng/mL or lower on two consecutive study visits, an interruption of treatment until serum ferritin was more than 500 ng/mL was considered. |
Countries
Belgium, Canada, France, Germany, Italy, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| β-thalassemia Patients Deferasirox (5-40 mg/kg/day) | 85 |
| Rare Anemias Patients Deferasirox (5-40 mg/kg/day) | 99 |
| Total | 184 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Laboratory Values | 0 | 1 |
| Overall Study | Administrative problems | 1 | 0 |
| Overall Study | Adverse Event | 7 | 14 |
| Overall Study | Condition no longer requires study drug | 0 | 8 |
| Overall Study | Death | 2 | 12 |
| Overall Study | Lost to Follow-up | 0 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Stopped at end of core | 3 | 9 |
| Overall Study | Stopped at end of extension 1 | 1 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 9 | 2 |
| Overall Study | Withdrawal by Subject | 9 | 15 |
Baseline characteristics
| Characteristic | Rare Anemias Patients | β-thalassemia Patients | Total |
|---|---|---|---|
| Age Continuous | 43.7 years STANDARD_DEVIATION 26.13 | 24.7 years STANDARD_DEVIATION 10.03 | 35.0 years STANDARD_DEVIATION 22.4 |
| Age, Customized >=65 years | 30 participants | 0 participants | 30 participants |
| Age, Customized <6 years | 9 participants | 2 participants | 11 participants |
| Age, Customized Between 12 and 15 years | 5 participants | 8 participants | 13 participants |
| Age, Customized Between 16 and 49 years | 30 participants | 69 participants | 99 participants |
| Age, Customized Between 50 and 64 years | 19 participants | 1 participants | 20 participants |
| Age, Customized Between 6 and 11 years | 6 participants | 5 participants | 11 participants |
| Region of Enrollment Belgium | 12 participants | 4 participants | 16 participants |
| Region of Enrollment Canada | 6 participants | 12 participants | 18 participants |
| Region of Enrollment France | 11 participants | 9 participants | 20 participants |
| Region of Enrollment Germany | 23 participants | 2 participants | 25 participants |
| Region of Enrollment Italy | 26 participants | 31 participants | 57 participants |
| Region of Enrollment United Kingdom | 0 participants | 12 participants | 12 participants |
| Region of Enrollment United States | 21 participants | 15 participants | 36 participants |
| Sex: Female, Male Female | 48 Participants | 43 Participants | 91 Participants |
| Sex: Female, Male Male | 51 Participants | 42 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 84 / 85 | 96 / 99 |
| serious Total, serious adverse events | 36 / 85 | 50 / 99 |
Outcome results
Primary
The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths
Safety was assessed using reports of adverse events of all participants in this study. Serious adverse events are those events that resulted in death, were life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or was a congenital anomaly/birth defect.
Time frame: Core study Baseline to the end of the study (up to 60 months)
Population: The safety analysis set comprised all participants who received at least one dose of deferasirox during either the core or extension studies.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| β-thalassemia Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Adverse Events | 85 Participants |
| β-thalassemia Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Serious Adverse Events | 36 Participants |
| β-thalassemia Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Deaths | 2 Participants |
| Rare Anemias Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Adverse Events | 99 Participants |
| Rare Anemias Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Serious Adverse Events | 50 Participants |
| Rare Anemias Patients | The Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs) or Deaths | Deaths | 12 Participants |
Secondary
The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study
Liver iron concentration was monitored at the end of the core study and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant. Pediatric participants or participants with a medical contraindication to liver biopsy were allowed the use of SQUID in the extension study.
Time frame: Core study Baseline to end of extension study (up to 60 months)
Population: The FAS comprised all participants who received at least one dose of deferasirox during either the core or extension studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| β-thalassemia Patients | The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study | 0.19 mg Fe/g dw | Standard Deviation 8.577 |
| Rare Anemias Patients | The Absolute Change in Liver Iron Content (LIC) as Assessed by Superconducting Quantum Interference Device (SQUID) From Baseline to End of Study | -2.04 mg Fe/g dw | Standard Deviation 4.521 |
Secondary
The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study
Serum ferritin was monitored monthly and the dose of deferasirox was increased or decreased in steps of 5 to 10 mg/kg/day up to a maximum of 40 mg/kg/day if appropriate, every 3 months. If serum ferritin fell to 500 ng/mL or lower on two consecutive study visits, an interruption of treatment until serum ferritin was more than 500 ng/mL was considered.
Time frame: Core study Baseline to end of extension study (up to 60 months)
Population: The FAS comprised all participants who received at least one dose of deferasirox during either the core or extension studies.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| β-thalassemia Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | Baseline | 4320.6 μg/L | Standard Deviation 2881.08 |
| β-thalassemia Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | End of Study | 3708.2 μg/L | Standard Deviation 3018.1 |
| β-thalassemia Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | Absolute Change | -612.4 μg/L | Standard Deviation 2520.87 |
| Rare Anemias Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | Baseline | 3268.8 μg/L | Standard Deviation 2082.6 |
| Rare Anemias Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | End of Study | 2896.0 μg/L | Standard Deviation 2597.22 |
| Rare Anemias Patients | The Absolute Change in Serum Ferritin (μg/L) Levels From Baseline to the End of the Study | Absolute Change | -382.2 μg/L | Standard Deviation 2325.41 |
Secondary
The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study
Liver iron concentration was monitored at the start of the core study, the end of the core study, and then at the end of the extension study. High-risk participants, like participants with rare anemia, were excluded from any further potential liver biopsy, except if required and justified by the Investigator for the general care of the participant.
Time frame: Core study Baseline to end of extension study (up to 60 months)
Population: The full analysis Set (FAS) comprised all participants who received at least one dose of deferasirox during either the core or extension studies.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| β-thalassemia Patients | The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study | -5.17 mg Fe/g dw | Standard Deviation 11.659 |
| Rare Anemias Patients | The Change in Liver Iron Content (LIC) as Assessed by Liver Biopsy at Baseline to the End of the Study | -5.10 mg Fe/g dw | Standard Deviation 7.756 |