Liver Iron Overload
Conditions
Keywords
iron overload, iron chelation therapy, B-thalassemia
Brief summary
The purpose of this study is to assess the safety and the effects on liver iron of Deferasirox when given for a long treatment period in patients with transfusion dependent iron overload.
Interventions
DRUGDeferasirox
10 mg/kg or 30 mg/kg orally daily
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients Currently participating in the 9-month comparative prolongation of extension phase of the original study. * Patients currently participating in the food-effect sub-study, according to amendment 3. * Ability to provide written informed consent prior to participation in this non-comparative extension study. * Female patients 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. * Body weight of at least 35 kg.
Exclusion criteria
* Pregnant or breastfeeding patients. * History of non-compliance to medical regimens and patients who are considered potentially unreliable. * Proteinuria \> 300 mg/L second void morning urine. * Patients with serum creatinine above the upper limit normal. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox | Baseline to 7 Years | The mean percentage change in liver iron content (LIC) as assessed by superconducting quantum interference device (SQUID) was evaluated by comparing the LIC at the start of Deferasirox treatment to the LIC at the end of the 5 year extension study for participants who were treated with Deferasirox for more than 3.5 years. LIC is expressed in milligrams of iron per gram of liver dry weight (mgFe/g dw). Relative change = 1- (Change in LIC from Baseline/Baseline level) x 100. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Relative Change in Serum Ferritin From Baseline to 3.5 Years | Baseline to 3.5 years | The mean percentage change in serum ferritin was evaluated by comparing the serum ferritin level at the start of Deferasirox treatment to the serum ferritin level collected 18 months following the start of the extension study. Serum ferritin is measured in micrograms per Liter. Relative Change = 1- (Change in ferritin level from Baseline/Baseline level) x 100. |
Countries
Italy
Participant flow
Recruitment details
This 5 year extension study includes participants treated in one or more studies: a 1 year main study to evaluate the safety,tolerability and the effects of 2 doses of deferasirox on liver iron content in comparison to standard chelation therapy with DFO, a 3 week food effect sub-study and a 12-21 month prolongation phase(NCT00379483).
Participants by arm
| Arm | Count |
|---|---|
| Deferasirox Deferasirox group consists of all participants who were initially randomized to 10 mg/kg or 20 mg/kg deferasirox orally daily in the main study and remained on deferasirox treatment during the comparative prolongation study (NCT00379483) and at the beginning of the 5-year non-comparative extension study | 51 |
| Deferasirox Crossover Deferasirox Crossover group consists of participants who were initially randomized to 40 mg/kg/day deferoxamine (DFO) subcutaneously in the main study and comparative prolongation study and crossed over to 5 mg to 30 mg/kg/day deferasirox orally daily at the beginning of the 5-year non-comparative extension study | 19 |
| Total | 70 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal Laboratory Value | 1 | 0 |
| Overall Study | Abnormal test procedure | 0 | 1 |
| Overall Study | Adverse Event | 9 | 4 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Stopped at end of Extension 1 | 2 | 0 |
| Overall Study | Stopped at end of prolongation visit 1 | 1 | 0 |
| Overall Study | Unsatisfactory therapeutic effect | 14 | 4 |
| Overall Study | Withdrawal by Subject | 9 | 6 |
Baseline characteristics
| Characteristic | Deferasirox | Deferasirox Crossover | Total |
|---|---|---|---|
| Age Continuous | 24.7 years STANDARD_DEVIATION 5.43 | 23.8 years STANDARD_DEVIATION 3.76 | 24.5 years STANDARD_DEVIATION 5.02 |
| Age, Customized 16 to 49 | 50 participants | 19 participants | 69 participants |
| Age, Customized 50 to 65 years | 1 participants | 0 participants | 1 participants |
| Region of Enrollment Italy | 51 participants | 19 participants | 70 participants |
| Sex: Female, Male Female | 35 Participants | 10 Participants | 45 Participants |
| Sex: Female, Male Male | 16 Participants | 9 Participants | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 50 / 51 | 19 / 19 |
| serious Total, serious adverse events | 18 / 51 | 2 / 19 |
Outcome results
Primary
The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox
The mean percentage change in liver iron content (LIC) as assessed by superconducting quantum interference device (SQUID) was evaluated by comparing the LIC at the start of Deferasirox treatment to the LIC at the end of the 5 year extension study for participants who were treated with Deferasirox for more than 3.5 years. LIC is expressed in milligrams of iron per gram of liver dry weight (mgFe/g dw). Relative change = 1- (Change in LIC from Baseline/Baseline level) x 100.
Time frame: Baseline to 7 Years
Population: All participants in the full analysis set treated with deferasirox for more than 3.5 years.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Deferasirox | The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox | -21.9 Percent change | Full Range 47.11 |
| Deferasirox Crossover | The Relative Change From Baseline in Liver Iron Content (LIC) After Prolonged Use of Deferasirox | -23.1 Percent change | Full Range 33.38 |
Secondary
Relative Change in Serum Ferritin From Baseline to 3.5 Years
The mean percentage change in serum ferritin was evaluated by comparing the serum ferritin level at the start of Deferasirox treatment to the serum ferritin level collected 18 months following the start of the extension study. Serum ferritin is measured in micrograms per Liter. Relative Change = 1- (Change in ferritin level from Baseline/Baseline level) x 100.
Time frame: Baseline to 3.5 years
Population: All participants comprised of the full analysis set were evaluated for the change in serum ferritin.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Deferasirox | Relative Change in Serum Ferritin From Baseline to 3.5 Years | 32.4 Percent change |
| Deferasirox Crossover | Relative Change in Serum Ferritin From Baseline to 3.5 Years | 33.2 Percent change |