Transfusional Iron Overload in β-thalassemia
Conditions
Keywords
β-thalassemia, iron overload, deferasirox
Brief summary
A 1-year randomized Phase III core trial (NCT00061750) using deferoxamine as the comparator was conducted to investigate the efficacy of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older. Patients who successfully completed this main trial may continue in this extension trial to receive chelation therapy with deferasirox for an additional 4 years. The objective of this study is to assess the efficacy and long-term safety of deferasirox in regularly transfused patients with β-thalassemia 2 years of age and older.
Interventions
DRUGDeferasirox
Tablets taken orally once a day.
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 who completed the 12-month core study (NCT00061750) * Female patients after menarche and who were sexually active, if they used double-barrier contraception, oral contraceptive plus barrier contraceptive, or had 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 * Patients with a history of non-compliance to medical regimens or those considered to be potentially unreliable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | up to 5 years | Adverse events results are based on preferred terms with at least 7% of participants in any group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Mean absolute change of LIC from start of Deferasirox (ICL670) treatment to the end of study assessed by liver biopsy. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw). |
| Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Mean absolute change in LIC from start of Deferasirox (ICL670) treatment to the end of the study assessed by Superconducting Quantum Interfering Device (SQUID) measurement used as a non-invasive alternative to Biopsy for pediatric participants. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw). |
| Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Mean Absolute Change in serum ferritin (ug/L) from start of treatment with Deferasirox (ICL670) to end of study taking into account the therapeutic goal which will either be to maintain iron balance or to induce negative iron balance. End of study taken as the mean of, at most, the last three available results after start of treatment with ICL670. |
| Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Measurement of the relative change in percent of potential surrogate marker: Serum Transferrin (g/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Transferrin at the End of Study-Serum Transferrin at Start of ICL670)/Serum Transferrin at Start of ICL670\*100. |
| Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Measurement of the relative change of potential surrogate markers: Serum Iron (µmol/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Iron at the End of Study-Serum Iron at Start of ICL670)/Serum Iron at Start of ICL670\*100. |
| Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Measurement of the relative change of potential surrogate marker: Transferrin Saturation (Percent) from start of treatment with Deferasirox (ICL670) to end of study. (Transferrin Saturation at the End of Study-Tranferrin Saturation at Start of ICL670)/Transferrin Saturation at Start of ICL670\*100. |
| Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Measurement of median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through biopsy. Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw). |
| Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Relative change in liver iron content (LIC) as measured by biopsy and calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value. |
| Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Measurement of the median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through Superconducting Quantum Interfering Device (SQUID). Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw). |
| Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Relative change in liver iron content (LIC) measured by Superconducting Quantum Interfering Device (SQUID), calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value. |
| Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study | Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years) | Median change in TBIE (mg/kg/day) from start of treatment with Deferasirox (ICL670) to end of study. |
Countries
Argentina, Belgium, Brazil, Canada, France, Germany, Greece, Italy, Tunisia, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study is an extension of core study (NCT0061750). 555 participants were treated with Deferasirox (ICL670) in the core and/or extension study. In the core study, 296 participants were treated with ICL670 and 259 participants were treated with Deferoxamine(DFO).
Participants by arm
| Arm | Count |
|---|---|
| Crossover Participants treated with Deferoxamine (DFO) during the core study and crossed over to receive Deferasirox (ICL670) orally once a day during the extension study. Dosage based on body weight. | 259 |
| ICL670 Participants treated with Deferasirox (ICL670) orally once a day during the core study and continued this treatment in the extension study. Dosage based on body weight. | 296 |
| Total | 555 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Abnormal laboratory value(s) | 6 | 3 |
| Overall Study | Abnormal test procedure result(s) | 0 | 1 |
| Overall Study | Administrative problems | 1 | 1 |
| Overall Study | Adverse Event | 16 | 27 |
| Overall Study | Death | 2 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 2 |
| Overall Study | Stopped at end of core | 0 | 32 |
| Overall Study | Stopped at end of extension 1 | 0 | 1 |
| Overall Study | Unsatisfactory therapeutic effect | 11 | 15 |
| Overall Study | Withdrawal by Subject | 32 | 30 |
Baseline characteristics
| Characteristic | Crossover | ICL670 | Total |
|---|---|---|---|
| Age Continuous | 18.3 years STANDARD_DEVIATION 9.82 | 17.1 years STANDARD_DEVIATION 9.46 | 17.7 years STANDARD_DEVIATION 9.64 |
| Race/Ethnicity, Customized Black or African American | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Oriental | 10 participants | 9 participants | 19 participants |
| Race/Ethnicity, Customized Other | 23 participants | 22 participants | 45 participants |
| Race/Ethnicity, Customized White | 225 participants | 263 participants | 488 participants |
| Sex: Female, Male Female | 125 Participants | 156 Participants | 281 Participants |
| Sex: Female, Male Male | 134 Participants | 140 Participants | 274 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 266 / 296 | 236 / 259 |
| serious Total, serious adverse events | 102 / 296 | 61 / 259 |
Outcome results
Primary
Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event
Adverse events results are based on preferred terms with at least 7% of participants in any group.
Time frame: up to 5 years
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Abdominal pain | 59 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Arthralgia | 39 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Cough | 85 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Upper respiratory tract infection | 32 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Nasopharyngitis | 56 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Transfusion reaction | 36 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Diarrhoea | 73 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Blood creatinine increased | 22 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Nausea | 52 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Gastroenteritis | 31 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Headache | 81 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Asthenia | 31 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Oropharyngeal pain | 50 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Rash | 24 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Urinary tract infection | 14 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Tonsillitis | 22 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pharyngitis | 57 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Fatigue | 22 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Vomiting | 61 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pain in extremity | 21 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Back Pain | 49 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Acute tonsillitis | 21 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pyrexia | 109 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Abdominal pain upper | 52 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Urticaria | 14 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Influenza | 65 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Toothache | 14 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Rhinitis | 45 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Sinusitis | 13 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Dyspepsia | 17 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Cholelithiasis | 11 Participants |
| Crossover | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Bronchitis | 41 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Cholelithiasis | 23 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Dyspepsia | 21 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pyrexia | 113 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Cough | 110 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Diarrhoea | 69 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Vomiting | 75 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Influenza | 70 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Abdominal pain | 75 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Nasopharyngitis | 73 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Nausea | 63 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Oropharyngeal pain | 62 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pharyngitis | 55 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Back Pain | 59 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Abdominal pain upper | 52 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Rhinitis | 52 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Bronchitis | 45 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Arthralgia | 45 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Upper respiratory tract infection | 52 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Transfusion reaction | 34 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Blood creatinine increased | 47 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Gastroenteritis | 37 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Asthenia | 31 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Rash | 34 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Tonsillitis | 30 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Fatigue | 29 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Pain in extremity | 30 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Acute tonsillitis | 29 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Urinary tract infection | 23 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Urticaria | 23 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Toothache | 22 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Sinusitis | 22 Participants |
| ICL670 | Long Term Safety and Tolerability Profile of ICL670 Based on the Number of Participants Who Experienced Any Adverse Event | Headache | 84 Participants |
Secondary
Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy
Measurement of median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through biopsy. Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Crossover | Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | -2.8 mg Fe/g dw | Full Range 8.23 |
| ICL670 | Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | -3.2 mg Fe/g dw | Full Range 10.31 |
Secondary
Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID
Measurement of the median absolute change in liver iron content (LIC) from start of treatment with Deferasirox (ICL670) to end of study obtained through Superconducting Quantum Interfering Device (SQUID). Absolute change = End of study value - start of treatment value. LIC is expressed in mg of iron per gram of liver dry weight (mg Fe/g dw).
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crossover | Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID | -1.1 mg Fe/g dw |
| ICL670 | Absolute Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by SQUID | -1.6 mg Fe/g dw |
Secondary
Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study
Measurement of the relative change of potential surrogate markers: Serum Iron (µmol/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Iron at the End of Study-Serum Iron at Start of ICL670)/Serum Iron at Start of ICL670\*100.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study | 1.5 Percent change | Standard Deviation 29.99 |
| ICL670 | Change in Surrogate Marker: Serum Iron From Start of Treatment With ICL670 to End of Study | 10.3 Percent change | Standard Deviation 39.07 |
Secondary
Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study
Measurement of the relative change in percent of potential surrogate marker: Serum Transferrin (g/L) from start of treatment with Deferasirox (ICL670) to end of study. (Serum Transferrin at the End of Study-Serum Transferrin at Start of ICL670)/Serum Transferrin at Start of ICL670\*100.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study | 7.7 Percent change | Standard Deviation 16.3 |
| ICL670 | Change in Surrogate Marker: Serum Transferrin From Start of Treatment With ICL670 to End of Study | 7.0 Percent change | Standard Deviation 14.78 |
Secondary
Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study
Measurement of the relative change of potential surrogate marker: Transferrin Saturation (Percent) from start of treatment with Deferasirox (ICL670) to end of study. (Transferrin Saturation at the End of Study-Tranferrin Saturation at Start of ICL670)/Transferrin Saturation at Start of ICL670\*100.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study | -5.4 Percent change | Standard Deviation 27.06 |
| ICL670 | Change in Surrogate Marker: Transferrin Saturation From Start of Treatment With ICL670 to End of Study | 3.4 Percent change | Standard Deviation 36.17 |
Secondary
Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study
Median change in TBIE (mg/kg/day) from start of treatment with Deferasirox (ICL670) to end of study.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crossover | Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study | 0.37 mg/kg/day |
| ICL670 | Change of Total Body Iron Excretion Rate (TBIE) From Start of ICL670 Treatment to the End of Study | 0.38 mg/kg/day |
Secondary
Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy
Mean absolute change of LIC from start of Deferasirox (ICL670) treatment to the end of study assessed by liver biopsy. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy | -2.4 mg Fe/g dw | Standard Deviation 8.23 |
| ICL670 | Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by Liver Biopsy | -4.1 mg Fe/g dw | Standard Deviation 10.31 |
Secondary
Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID
Mean absolute change in LIC from start of Deferasirox (ICL670) treatment to the end of the study assessed by Superconducting Quantum Interfering Device (SQUID) measurement used as a non-invasive alternative to Biopsy for pediatric participants. Reported in milligrams of Iron per gram dry weight (mg Fe/g dw).
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID | -0.5 mg Fe/g dw | Standard Deviation 5.34 |
| ICL670 | Long-term Effect of ICL670 on Hepatic Iron Stores Measured by Means of Liver Iron Content (LIC) as Assessed by SQUID | -0.7 mg Fe/g dw | Standard Deviation 4.03 |
Secondary
Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study
Mean Absolute Change in serum ferritin (ug/L) from start of treatment with Deferasirox (ICL670) to end of study taking into account the therapeutic goal which will either be to maintain iron balance or to induce negative iron balance. End of study taken as the mean of, at most, the last three available results after start of treatment with ICL670.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: All patients enrolled into core study and who consented to participate in extension contributed to the pool of data on long term safety follow-up. Analyses included all patients who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 patients from the core group who did not continue into extension.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Crossover | Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study | -122.1 μg/L | Standard Deviation 1406.77 |
| ICL670 | Long-term Effect of Treatment With ICL670 on the Changes in Serum Ferritin Levels From Start of ICL670 Treatment to End of Study | -527.8 μg/L | Standard Deviation 1852.12 |
Secondary
Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID
Relative change in liver iron content (LIC) measured by Superconducting Quantum Interfering Device (SQUID), calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC SQUID data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crossover | Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID | -20.8 percent of start value |
| ICL670 | Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study as Measured by SQUID | -33.0 percent of start value |
Secondary
Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy
Relative change in liver iron content (LIC) as measured by biopsy and calculated by: End of study value - Start of ICL670 treatment value (absolute change) / Start of ICL670 treatment value.
Time frame: Start of ICL670 treatment, End of Study or study discontinuation (up to 5 years)
Population: Population includes only those participants from the full analysis set (defined as all participants who received at least 1 dose of ICL670 in the core/extension study, that is, analyses also included ICL670 participants from the core group who did not continue into extension) and had LIC Biopsy data at Start of ICL670 treatment and End of Study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Crossover | Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | -25.4 percent of start value |
| ICL670 | Relative Change in Liver Iron Content From Start of ICL670 Treatment to End of Study Measured by Biopsy | -26.0 percent of start value |