E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated | |
E.1.1.1 | Medical condition in easily understood language |
•Transfusional Iron Overload
•β-thalassemia Major
•Pediatric Rare Anemia
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054661 |
E.1.2 | Term | Thalassemia major |
E.1.2 | System Organ Class | 100000004850 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10054660 |
E.1.2 | Term | Thalassemia beta |
E.1.2 | System Organ Class | 100000004850 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
•Participants With Adverse Events by Primary System Organ Class (SOC) [ Time Frame: 4 year extension + core 1 year ]
Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.
•Change in Liver Iron Concentration (LIC) [ Time Frame: Baseline of Core Study to End of Extension Study, up to 5 years. ]
Change in Liver Iron Concentration [LIC] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw)
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E.2.2 | Secondary objectives of the trial |
•Total Body Iron Elimination (TBIE) Rate (mg/kg/Day)
Elimination (TBIE) Rate [mg/kg/Day] was calculated for each patient based on SQUID ( Superconducting Quantum Interference Device) results.
•Relative Change in Serum Ferritin Level
Serum levels were drawn at the baseline of the Core Study up to 18 months of the Extension Study. Levels were analyzed for serum ferritin measured in micrograms per Liter. Relative change (%) in serum ferritin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in ferritin level from Baseline/Baseline level) x 100.
•Relative Change in Serum Transferrin Level
Serum Levels were drawn at Baseline of the Core Study and up to 18 months in the Extension Study. Serum was analyzed for transferrin levels measured as grams per Liter. Relative change (%) in serum transferrin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in transferrin level from Baseline/Baseline level) x 100. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Completion of the planned 12-month core trial, (NCT00390858).
•Female patients who have reached menarche and who were sexually active were to 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 from the parent or legal guardian in accordance with the national legislation.
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E.4 | Principal exclusion criteria |
•Pregnant or breast feeding patients
•Patients with a history of non-compliance to medical regimens and patients who are considered by the investigator as potentially unreliable.
Other protocol-defined exclusion criteria may apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
•Participants With Adverse Events by Primary System Organ Class (SOC)
Safety parameters were measured by the number and type of adverse events (AEs). An adverse event is any untoward medical occurence in a patient administered a medicinal product that does not necessarily have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign ( for example, an abnormal laboratory finding), symptom or disease temporally associated with the use of the medicinal product, whether or not this is associated with the use of this medicinal product.
•Change in Liver Iron Concentration (LIC)
Change in Liver Iron Concentration [LIC] measured by means of SQUID (Superconducting Quantum Interference Device). LIC is expressed in milligrams of iron per gram of liver dry weight (mg Fe/g dw) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
•Participants With Adverse Events by Primary System Organ Class (SOC) : 4 year extension + core 1 year
•Change in Liver Iron Concentration (LIC) : Baseline of Core Study to End of Extension Study, up to 5 years. |
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E.5.2 | Secondary end point(s) |
•Total Body Iron Elimination (TBIE) Rate (mg/kg/Day) [ Time Frame: Baseline of Core Study to End of Extension Study, up to 5 years ]
Total Iron Body Elimination (TBIE) Rate [mg/kg/Day] was calculated for each patient based on SQUID ( Superconducting Quantum Interference Device) results.
•Relative Change in Serum Ferritin Level [ Time Frame: Baseline of Core Study to Extension 18 months, up to 2.5 years. ]
Serum levels were drawn at the baseline of the Core Study up to 18 months of the Extension Study. Levels were analyzed for serum ferritin measured in micrograms per Liter. Relative change (%) in serum ferritin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in ferritin level from Baseline/Baseline level) x 100.
•Relative Change in Serum Transferrin Level [ Time Frame: Baseline of Core Study to Extension Study 18 months , up to 2.5 years ]
Serum Levels were drawn at Baseline of the Core Study and up to 18 months in the Extension Study. Serum was analyzed for transferrin levels measured as grams per Liter. Relative change (%) in serum transferrin level was assessed from Baseline to Extension 18 months. Relative Change = 1 - (Change in transferrin level from Baseline/Baseline level) x 100.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
•Total Body Iron Elimination (TBIE) Rate (mg/kg/Day) : Baseline of Core Study to End of Extension Study, up to 5 years
•Relative Change in Serum Ferritin Level: Baseline of Core Study to Extension 18 months, up to 2.5 years.
•Relative Change in Serum Transferrin Level: Baseline of Core Study to Extension Study 18 months , up to 2.5 years |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
Will this trial be conducted at a single site globally?
| No |
E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
E.8.6 Trial involving sites outside the EEA |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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February 2008 (final data collection date for primary outcome measure) |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |