E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic iron overload |
Accumulo cronico di ferro |
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E.1.1.1 | Medical condition in easily understood language |
Chronic iron overload |
Accumulo cronico di ferro |
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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 | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10065974 |
E.1.2 | Term | Chronic iron overload |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To assess the non-inferiority of Deferiprone compared to Deferasirox ìn terms of changes in ferritin levels and cardiac iron concentration |
Valutare la non-inferiorità del Deferiprone rispetto al Deferasirox in termini di contenimento dei livelli di ferritina e concentrazione cardiaca di ferro |
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E.2.2 | Secondary objectives of the trial |
1. to assess treatment efficacy in terms of ferritin levels 2. to assess treatment efficacy in terms of cardiac MRI T2* in patients over 10 years of age able to perform MRI scan without sedation 3. to estimate the efficacy of treatments in terms of liver iron concentration (LIC) measured by MRI in all paediatric subjects able to have MRI scan without sedation 4. to evaluate the safety and tolerability profile of treatments 5. to assess healthcare resources utilisation and patient global assessment, including compliance and quality of life evaluation 6. to confirm the relationship of demographic covariates and the disposition of DFP across the study population. |
1. Valutare l’efficacia del trattamento in termini di livelli di ferritina; 2. Valutare l’efficacia del trattamento in termini di MRI T2* cardiaca in pazienti di età superiore a 10 anni in grado di effettuare una scansione MRI senza sedazione; 3. Stimare l’efficacia del trattamento in termini di concentrazione epatica di ferro (LIC-Liver Iron Concentration) misurata tramite MRI in tutti i pazienti pediatrici in grado di effettuare una scansione MRI senza sedazione; 4. Valutare la sicurezza e la tollerabilità dei trattamenti; 5. Valutare l’utilizzo di risorse sanitarie, inclusa la valutazione della compliance ai trattamenti e della qualità di vita; 6. Confermare la relazioni esistenti fra variabili demografiche e distribuzione di DFP nella popolazione in studio. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients on current treatment with DFO or DFX or DFP in a chronic transfusion program receiving at least 150 mL/kg/year of packed red blood cells (corresponding approximately to 12 transfusions); 2. For patients naïve to chelation treatment: patients that have received at least 150 mL/kg of packed red blood cells (corresponding to approximately 12 transfusions) in a chronic transfusion program and with serum ferritin levels ≥ 800 ng/mL; 3. For patients aged from 1 month to less than 6 years: known intolerance or contraindication to deferoxamine; 4. Written informed consent and patient's informed assent to patient’s maturity and understanding |
1. Per pazienti attualmente in trattamento di chelazione con deferoxamina o DFX o DFP: soggetti inseriti in un programma di trasfusione cronica che ricevono almeno 150 ml/kg/anno di emazie concentrate (corrispondente approssimativamente a 12 trasfusioni); 2. Per pazienti non ancora in trattamento di chelazione (pazienti naïve): soggetti che hanno ricevuto almeno 150 mL/kg di emazie concentrate (corrispondente approssimativamente a 12 trasfusioni) inseriti un programma di trasfusioni croniche e con livelli di ferritina serica ≥ 800 ng/mL; 3. Per pazienti di età compresa tra 1 mese e 6 anni non compiuti: intolleranza o controindicazione nota verso deferoxamina; 4. Consenso informato scritto e assenso del bambino in relazione alla sua capacità di comprendere e alla sua maturità. |
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E.4 | Principal exclusion criteria |
1. Patients with known intolerance or contraindication to either DFP or DFX 2. Patients receiving DFX at a dose > 40 mg/kg/day or DFP at a dose > 100 mg/kg/day at screening 3. Platelet count <100.000/mm3 during the run-in phase 4. Absolute neutrophils count <1.500/mm3 during the run-in phase 5. Hb levels lower than 8g/dL during the run-in phase 6. Evidence of abnormal liver function 7. Iron overload from causes other than trasfusional haemosiderosis 8. Severe heart dysfunction secondary to iron overload 9. Serum creatinine level > ULN for age during the run-in phase 10. History of significant medical or psychiatric disorder 11. The patient has received another investigational drug within 30 days prior to this study 12. Fever and other signs/symptoms of infection in the 10 days before baseline assessment 13. Concomitant use of trivalent cation-dependent medicinal products such as aluminium-based antacids 14. Positive test for β-HCG |
1. Pazienti con intolleranza o controindicazione nota verso DFP o DFX; 2. Pazienti che ricevono DFX ad un dosaggio > 40 mg/kg/die o DFP ad un dosaggio > 100 mg/kg/die allo screening; 3. Conta delle piastrine <100.000/mm3 durante la fase di run-in; 4. Conta dei neutrofili <1.500/mm3 durante la fase di run-in; 5. Livelli di Hb < 8g/dL durante la fase di run-in; 6. Evidenza di anormalità nella funzione epatica; 7. Accumulo di ferro per cause diverse dalla emosiderosi da trasfusione; 8. Grave disfunzione cardiaca secondaria all’accumulo di ferro; 9. Livello di creatinina serica al di sopra dei valori normali per età durante la fase di run-in; 10. Manifestazioni pregresse di disordini medici o psichiatrici significativi; 11. Il paziente ha ricevuto un altro farmaco sperimentale nei 30 giorni precedenti l’inizio di questo studio; 12. Febbre o altri segni/sintomi di infezione nei 10 giorni precedenti la valutazione basale; 13. Uso concomitante di prodotti medicinali trivalenti cationi-dipendenti come antiacidi a base di alluminio. 14. Positività al test per β-HCG. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of successfully chelated patients assessed by serum ferritin levels (all patients) and cardiac MRI T2* (patients above 10 years of age able to have an MRI scan without sedation). |
Percentuale di pazienti chelati con successo, valutata attraverso i livelli di ferritina serica (in tutti i pazienti) e tramite MRI T2* cardiaca (in pazienti di età superiore a 10 anni in grado di eseguire una scansione MRI senza sedazione). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Serum ferritine will be measured every 3 months Cardiac MRI (Magnetic Resonance Imaging) T2* will be measured at month 1, 6 and 12 of treatment. Primary endpoint in terms of percentage of successfully chelated patients will be assessed as difference between basal and final (12 months) levels |
La ferritina serica verrà misurata ogni 3 mesi. La risonanza T2* cardiaca verrà misurata al mese 1, al mese 6 e al mese 12 di trattamento. L'endpoint primario come percentuale di successo verrà valutato sulle differenze tra i valori basali e quelli a 12 mesi |
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E.5.2 | Secondary end point(s) |
1. Liver iron concentration (LlC) as measured by MRI (Magnetic Resonance Imaging) in patients able to undergo MRI scan without sedation. 2. Safety and tolerability assessments 3. Quality of Life |
1. Concentrazione epatica di ferro (LIC) misurata con la Risonanza Magnetica (MRI) in pazienti capaci di effettuare la risonanza magnetica senza sedazione 2. Valutazione della sicurezza e tollerabilità 3. Qualità di vita |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. LCI will be assessed at baseline and at the end of treatment (12 months); 2. Adverse events (nature, severity, grade, duration) will be recorded monthly 3. Quality of Life will be assessed at month 1 and 12 of treatment. |
1. LIC sarà valutata al baseline ed alla fine del trattamento (12 mesi) 2. Gli eventi avversi (natura, severità, grado, durata) saranno registrati mensilmente. 3. La Qualità di vita sarà valutata al mese 1 e 12 di trattamento. |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life |
Qualità di vita |
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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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 12 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 24 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 24 |
E.8.9.2 | In all countries concerned by the trial days | 0 |