E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
congenital fibrinogen deficiency |
deficit congenito di fibrinogeno |
|
E.1.1.1 | Medical condition in easily understood language |
deficency of fibrinogen in human plasma |
deficit di fibrinogeno nel plasma umano |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
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 determine the single dose pharmacokinetics of Octafibrin and Haemocomplettan® P/RiaSTAPTM in subjects with congenital fibrinogen deficiency
• To determine maximum clot strength (maximum clot firmness [MCF]) as a surrogate marker for haemostatic efficacy before and after
administration of Octafibrin and Haemocomplettan® P/ RiaSTAPTM in
subjects with congenital fibrinogen deficiency |
Determinare la farmacocinetica della singola dose di Octafibrin e
Haemocomplettan ® P / RiaSTAPTM in soggetti con deficit congenito di fibrinogeno
Determinare la stabilità massima del coagulo (maximum clot firmness [MCF]) come marker surrogato per l'efficacia emostatica prima e dopo la somministrazione di Octafibrin ed Haemocomplettan ® P / RiaSTAPTM in
soggetti con deficit congenito del fibrinogeno |
|
E.2.2 | Secondary objectives of the trial |
To assess the safety of Octafibrin in subjects with congenital fibrinogen deficiency |
Valutare la sicurezza di Octafibrin in soggetti con deficit congenito di fibrinogeno |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Subject age ≥12 years
• Documented congenital fibrinogen deficiency (afibrinogenaemia)
Plasma fibrinogen activity and antigen at screening bellow detection limit (i.e. <20mg/dl)
• Informed consent signed by subject or legal guardian |
età ≥ 12 anni
deficit congenito di fibrinogeno documentato (afibrinogenaemia)
Attività plasmatica del fibrinogeno e antigene allo screening al di sotto del limite di rilevamento (cioè <20mg/dl)
consenso informato firmato dal soggetto o dal suo rappresentante legale |
|
E.4 | Principal exclusion criteria |
• Life expectancy <6 months
• Bleeding disorder other than congenital fibrinogen deficiency
• Dysfibrinogenemia
• Treatment with:
Any fibrinogen concentrate or other fibrinogen-containing blood product in the 2 weeks prior to enrolment
• Presence or history of:
Hypersensitivity to study medication
Deep vein thrombosis or pulmonary embolism within 1 year prior to enrolment
Arterial thrombosis within 1 year prior to enrolment
Hypersensitivity to human plasma proteins
Acute bleeding
History of oesophageal varicose bleeding
End-stage liver disease (i.e. Child-Pugh-score B or C)
Planned major surgery with a need for blood transfusion during the PK blood-sampling period of this study
Pregnancy, or an intention to become pregnant during the study
Currently breast-feeding, or with the intention of breast-feeding during the study
HIV positive with a viral load >200 particles/μl ~ >400000 copies/ml
Polytrauma 1 year prior to enrolment
Suspicion of an anti-fibrinogen inhibitor as indicated by previous in-vivo recovery, if available <0.5 (mg/dl)/(mg/kg), (there is currently no standard test for inhibitors)
Blood or plasma donation in the 3 months prior to enrolment
|
Aspettativa di vita < di sei mesi
Disturbo della coagulazione differente dal deficit congenito del fibrinogeno
Disfibrinogenemia
Terapia con:
- qualsiasi concentrato di fibrinogeno o altro prodotto ematico
contenente fibrinogeno nelle due settimane precedenti il reclutamento
Presenza o storia di:
- ipersensibilità al farmco in studio
- trombosi venosa profonda o embolia polmonare entro l'anno
precedente il reclutamento
- trombosi arteriosa entro l'anno precedente il reclutamento
- ipersensibilità alle proteine plasmatiche umane
emorragia acuta
storia di emorragia varicosa esofagea
patologia epatica all'ultimo stadio (con punteggio Child-Pugh B o C)
Importante intervento chirurgico programmato con necessità di
trasfusione ematica durante il priodo di campionamento ematico
farmacocinetico di questo studio
Gravidanza, o un'intenzione di avviare una gravidanza durante lo studio
Allattamento, o l'intenzione di avviare l'allattamento durante lo studio
HIV positivo con carico virale > di 200 particelle/μl ~ >400000
copies/ml
Politrauma 1 anno prima del reclutamento
Sospetto di inibitore anti-fibrinogeno come indicato da precedente ripreso in-vivo, se disponibile <0.5 (mg/dl)/(mg/kg), (non sono
attualmente disponibili test standard per gli inibitori)
Donazione di sangue o plasma nei tre mesi precedenti il reclutamento |
|
E.5 End points |
E.5.1 | Primary end point(s) |
A comparison of the AUC between Octafibrin and Haemocomplettan®
P/RiaSTAPTM
Surrogate endpoint for haemostatic efficacy
Comparison of MCF between Octafibrin and Haemocomplettan®
P/RiaSTAPTM at 1 hour post-infusion |
Un confronto dell'AUC tra Octafibrina e Haemocomplettan®
P/RiaSTAPTM
Endpoint surrogato per l'efficacia emostatica:
Confronto della MCF tra Octafibrina ed Haemocomplettan® P/RiaSTAPTM
a 1 ora dopo l'infusione |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
at baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 and 312 hours postinfusion. |
al basale, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 e 312 ore dopo l'infusione |
|
E.5.2 | Secondary end point(s) |
• To compare the in vivo recovery between Octafibrin and
Haemocomplettan® P/ RiaSTAPTM
• To compare the pharmacokinetics between Octafibrin and
Haemocomplettan® P/ RiaSTAPTM
• To document the safety of Octafibrin |
Confrontare il recupero in vivo tra Octafibrina ed Haemocomplettan®
P/ RiaSTAPTM
Confrontare la farmacocinetica tra Octafibrina ed Haemocomplettan®
P/ RiaSTAPTM
Documentare la sicurezza di Octafibrina |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
at baseline, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 and 312 hours postinfusion. |
al basale, 0.5, 1, 2, 4, 8, 24, 48, 96, 144, 216 e 312 ore dopo l'infusione |
|
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 | Yes |
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) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | Yes |
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) | No |
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 | No |
E.8.1.6 | Cross over | Yes |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Bulgaria |
Germany |
Iran, Islamic Republic of |
Italy |
Spain |
Turkey |
United Kingdom |
United States |
|
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
|
LAST PATIENT LAST VISIT |
ULTIMA VISITA DELL'ULTIMO PAZIENTE |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
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 | 2 |
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 |