E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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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 | SOC |
E.1.2 | Classification code | 10010331 |
E.1.2 | Term | Congenital, familial and genetic disorders |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10005329 |
E.1.2 | Term | Blood and lymphatic system disorders |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 |
The primary objective of the study is to evaluate the long-term safety of rFVIIIFc in subjects with hemophilia A. |
L' obiettivo primario è quello di valutare la sicurezza a lungo termine di rFVIIIFc in soggetti affetti da emofilia A. |
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E.2.2 | Secondary objectives of the trial |
The secondary objective of the study is to evaluate the efficacy of rFVIIIFc in the prevention and treatment of bleeding episodes in subjects with hemophilia A. |
L' obiettivo secondario di questo studio è quello di valutare l' efficacia di rFVIIIFc nella prevenzione e nel trattamento di episodi emoraggici in soggetti affetti da emofilia A. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
To be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of signing the informed consent at Visit 1 of the study: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations. Parental or guardian consent is required for subjects who are less than 18 years of age or unable to give consent, or as applicable per local laws. Subjects who are less than 18 years of age may provide assent in addition to the parental/guardian consent, if appropriate. 2. Subjects who have completed the studies 997HA301, 8HA02PED, or other Phase 3 studies with rFVIIIFc. |
Per essere ritenuti idonei a partecipare a questo studio, al momento della firma del modulo di consenso informato in occasione della Visita 1 dello studio i candidati devono soddisfare i seguenti criteri di idoneità: 1. Capacità di comprendere lo scopo e i rischi associati allo studio, fornire un consenso informato datato e firmato e l’autorizzazione all’utilizzo di informazioni sanitarie protette (PHI) in conformità con le normative nazionali e locali riguardanti la privacy del soggetto. Per i soggetti di età inferiore ai 18 anni o che non sono in grado di fornire il loro consenso, è richiesto il consenso dei genitori o del tutore, secondo quanto richiesto dalle leggi applicabili. I soggetti di età inferiore ai 18 anni possono fornire, ove appropriato, il consenso in aggiunta a quello dei genitori/del tutore. 2. I soggetti che hanno completato gli studi 997HA301, 8HA02PED o altri studi di Fase 3 con rFVIIIFc. |
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E.4 | Principal exclusion criteria |
Candidates will be excluded from study entry if any of the following exclusion criteria exist at the time of signing the informed consent at Visit 1 of the study: 1. Confirmed positive high-titer inhibitor test (≥5.00 BU/mL) 2. Medical or other reasons that, in the opinion of the Investigator, make the subject unsuitable for enrollment. |
I soggetti verranno esclusi dallo studio nel caso in cui sussista uno dei seguenti criteri di esclusione al momento della firma del modulo del consenso informato in occasione della Visita 1 dello studio: 1. Test inibitore confermato a titolo alto positivo (≥5,00 BU/ml) 2. Motivazioni mediche o di altro tipo che, a giudizio dello sperimentatore, rendano il soggetto non idoneo all’arruolamento. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The frequency of inhibitor development |
La frequenza dello sviluppo dell'inibizione |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
On every scheduled clinic visit by Nijmegen-modified Bethesda Assay |
Ogni visita prevista dalla valutazione ''Nijmegen-modified Bethesda Assay'' |
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E.5.2 | Secondary end point(s) |
The number of annualized bleeding episodes (spontaneous and traumatic) per subject The number of annualized spontaneous joint bleeding episodes per subject The total number of days of exposure per subject per year The mean dose of rFVIIIFc per kg per subject per year per treatment regimen Physician‟s global assessment of response to treatment using a 4-point scale Subject‟s assessment of response to treatment using a 4-point scale The incidence of adverse events (AEs) and serious adverse events (SAEs) |
Il numero di episodi emorragici in un anno (spontanei e traumatici) per soggetto. Il numero di episodi emorragici articolari spontanei in un anno per soggetto. Il numero totale di giorni per esposizione in un anno per soggetto. La dose media annua di rFVIIIFc per kg per soggetto per regime di trattamento.Valutazione globale del medico di risposta al trattamento utilizzando una scala a 4 punti. L' incidenza degli eventi avversi ed eventi avversi gravi. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The bleeding episodes, the number of treatment days and the mean dose of rFVIIIFc per kg per subject will be monitored by the physician on an ongoing basis, by reviewing patient eDiary information. The physician and subject assessment of response will be taken at every clinic visit. AE and SAE information will be collected at every clinic visit and in the infrequent visit period follow up calls to the patient every 2 months. |
Gli episodi di sanguinamento, il numero di giorni di trattamento e la dose media di rFVIIIFc per kg per soggetto saranno monitorati dal medico su base continuativa, rivedendo le informazioni sull' eDiary del paziente. Le valutazioni di risposta del medico e del soggetto verranno ottenute ad ogni visita clinica e durante non frequenti chiamate nel periodo di follow up al paziente ogni due mesi. |
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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 | Yes |
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 | Yes |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
to evaluate different treatement regimens |
valutare i diversi regimi di trattamento |
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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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
studio di estensione |
extension study |
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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 | Yes |
E.8.2.3.1 | Comparator description |
4IMPs con diversi dosaggi |
4IMPs with different doses |
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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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Australia |
Brazil |
Canada |
Chile |
China |
Hong Kong |
India |
Israel |
Japan |
New Zealand |
Russian Federation |
South Africa |
United States |
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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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Last visit last subject |
Ultima visita dell' ultimo paziente |
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |