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 |
Bleeding disorder, inherited deficiency in clotting factor VIII |
Disordine della coagulazione di tipo ereditario a carico del fattore VIII |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
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 | 10018938 |
E.1.2 | Term | Haemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
|
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 evaluate immunogenicity of NNC 0129-0000-1003 (hereafter referred
to as N8-GP) |
Valutare l'immunogenicità di NNC 0129-0000-1003 (d'ora in poi chiamato N8-GP) |
|
E.2.2 | Secondary objectives of the trial |
To evaluate safety other than immunogenicity of N8-GP
- To evaluate efficacy of N8-GP in prophylaxis and treatment of bleeding
episodes
- To evaluate pharmacokinetic properties of N8-GP and compare to
previous FVIII product |
• Valutare la sicurezza oltre che l’immunogenicità di N8-GP
• Valutare l’efficacia di N8-GP nella profilassi e nel trattamento degli episodi emorragici
• Valutare le proprietà farmacocinetiche di N8-GP e confrontarle al precedente prodotto a base di FVIII (solo valutazioni PK) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male patients with severe congenital haemophilia A (FVIII activity level
< 1%)
- Age below 12 years
- Weight ≥10 kg
- Documented history of > 150 ED to FVIII products for patients aged 6-
11 years and > 50 ED to FVIII products for patients aged 0-5 years |
• Pazienti di sesso maschile affetti da emofilia A congenita (livello di attività del FVIII < 1%)
• Età inferiore ai 12 anni
• Peso > 10 kg
• Anamnesi documentata di > 150 ED a prodotti a base di FVIII per i pazienti di età compresa tra 6 ed 11 anni e > 50 ED a prodotti a base di FVIII per i pazienti di età compresa tra 0 e 5 anni |
|
E.4 | Principal exclusion criteria |
Anamnesi di sviluppo di inibitori del FVIII |
Any history of FVIII inhibitors |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of inhibitory antibodies against coagulation factor VIII (FVIII)
≥0.6 Bethesda units |
• Incidenza degli anticorpi inibitori anti-FVIII ≥ 0,6 unità Bethesda (BU) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During the main phase of the trial (from 0-26 weeks of treatment) |
durante la fase principale dello studio (da 0 a 26 settimane di trattamento) |
|
E.5.2 | Secondary end point(s) |
1. Frequency of adverse events including serious adverse events
reported during the trial period
2. Haemostatic effect of N8-GP when used for treatment of bleeding
episodes and assessed as: Excellent, Good, Moderate, or None
3. Number of bleeding episodes during prophylactic treatment with N8-
GP (annualised bleeding rate)
4. Consumption of N8-GP per bleeding episode (number of injections and
U/kg)
5. Consumption of N8-GP during prophylaxis (number of injections and
U/kg per month and year)
6. Incremental recovery (defined as the peak level recorded 30 min after
end of injection) evaluated for previous FVIII product and N8-GP
7. Area under the curve evaluated for previous FVIII product and N8-GP
8. Terminal half-life evaluated for previous FVIII product and N8-GP
9. Clearance evaluated for previous FVIII product and N8-GP |
1.Frequenza degli eventi avversi inclusi gli eventi avversi gravi seri segnalati durante il periodo dello studio
2. Effetto emostatico di N8-GP quando utilizzato per il trattamento di episodi emorragici e valutato come: Eccellente, Buono, Moderato o Nessuno
3. Numero degli episodi emorragici durante il trattamento profilattico con N8-GP (tasso annuale di sanguinamento)
4. Consumo di N8-GP per episodio emorragico (numero di iniezioni e U/kg)
5. Consumo di N8-GP durante la profilassi (numero di iniezioni e U/kg per mese e per anno)
6. recupero incrementale (definito come il livello massimo analizzato 30 minuti dopo l'iniezione) valutato sia per il precedente prodotto a base di fattore VIII che per N8-GP
7. Area sotto la curva (AUC) valutata sia per il precedente prodotto a base di fattore VIII che per N8-GP
8. Emivita terminale valutata sia per il precedente prodotto a base di fattore VIII che per N8-GP
9. clearance valutata sia per il precedente prodotto a base di fattore VIII che per N8-GP |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
The pharmacokinetic endpoints on previous FVIII product will be based
on assessments performed 2-6 weeks prior to initial dosing with N8-GP
and up to 30 hours after administration of previous FVIII product.
The pharmacokinetic endpoints on N8-GP will be based on assessments
performed from 1 hour prior to and up to 96 hours after initial
administration of N8-GP.
All secondary safety and efficacy endpoints will be analysed and
reported separately for the main phase (from 0-26 weeks of treatment)
and the extension phase of the trial (from 26 weeks to the last patient
has completed the trial). |
Gli endpoint di farmacocinetica sul precedente prodotto a base di fattore VIII saranno basati su esami effettuati 2-6 settimane prima del dosaggio iniziale con N8-GP e fino a 30 ore dopo la somministrazione del precedente prodotto a base di fattore VIII.
Gli endpoint di farmacocinetica su N8-GP saranno basati su esami effettuati da 1 ora prima della somministrazione di N8-GP fino a 96 ore dalla somministrazione di N8-GP.
Tutti gli endpoint secondari di safety ed efficacia saranno analizzati e riportati separatamente per la fase principale (da 0 a 26 settimane di trattamento) e la fase di estensione (dalla settimana 26 fino al completamento del trial da parte dell'ultimo paziente). |
|
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity |
Immunogenicità |
|
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 45 |
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 |
European Union |
Australia |
Brazil |
Canada |
Israel |
Japan |
Korea, Republic of |
Macedonia, the former Yugoslav Republic of |
Malaysia |
Switzerland |
Turkey |
Ukraine |
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
|
|
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 | 63 |
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 | 63 |
E.8.9.2 | In all countries concerned by the trial days | 0 |