E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A |
Hemofilia A |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding disorder, inherited deficiency in clotting factor VIII |
Desorden de sangrado, deficiencia heredada en el factor VIII de coagulación |
|
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 | 16.1 |
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 N8-GP (turoctocog alfa pegol) in previously untreated patients (PUPs) with severe haemophilia A |
Evaluar la inmunogeneicidad de N8-GP (turoctocog alfa pegol) en pacientes no tratados previamente (PNTP)con hemofilia A grave |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate safety other than immunogenicity of N8-GP (turoctocog alfa pegol) in PUPs with severe haemophilia A - To evaluate efficacy of N8-GP (turoctocog alfa pegol) in PUPs with severe haemophilia A o in long-term prophylaxis treatment (bleeding preventive effect) o in the treatment of bleeding episodes |
?Evaluar la seguridad, excepto la inmunogenia inmunogenicidad de N8-GP (turoctocog alfa pegol) en PNTP con hemofilia A grave ?Evaluar la eficacia de N8-GP (turoctocog alfa pegol) en PNTP con hemofilia A grave o en el tratamiento profiláctico a largo plazo (efecto preventivo de las hemorragias) oen el tratamiento de los episodios hemorrágicos |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial - Male, age < 6 years at the time of signing informed consent - Diagnosis of severe haemophilia A (factor VIII activity level < 1%) based on medical records or central laboratory results - No prior use of purified clotting factor products (5 previous exposure to blood components is acceptable) |
?Obtención del consentimiento informado antes de realizar cualquier actividad relacionada con el ensayo. Se consideran actividades relacionadas con el ensayo todos los procedimientos que se lleven a cabo como parte del ensayo, incluidas las actividades para determinar la idoneidad para el mismo. ?Pacientes varones menores de 6 años de edad en el momento de la firma del consentimiento informado. ?Diagnóstico de hemofilia A grave (actividad del factor VIII < 1%) basado en la historia clínica o los resultados del laboratorio central. ?Ausencia de tratamiento previo con productos purificados de factores de la coagulación (se aceptan 5 exposiciones previas a hemoderivados) |
|
E.4 | Principal exclusion criteria |
- Any history of FVIII inhibitor (defined by medical records) - Known or suspected hypersensitivity to trial product or related products - Previous participation in this trial. Participation is defined as administration of trial product - Receipt of any investigational medicinal product within 30 days before screening - Congenital or acquired coagulation disorder other than haemophilia A. Any chronic disorder or severe disease which, in the opinion of the Investigator, might jeopardise patient?s safety or compliance with the protocol. - Patient?s parent(s)/legally acceptable representative(s) mental incapacity, unwillingness to cooperate, or a language barrier precluding adequate understanding and cooperation |
?Antecedentes de uso de inhibidores del FVIII (según la historia clínica). ?Hipersensibilidad conocida o presunta al producto del ensayo o productos relacionados. ?Participación previa en este ensayo. La participación se define como la administración del producto del ensayo. ?Recepción de cualquier producto en investigación en los 30 días previos a la selección ?Trastornos de la coagulación congénitos o adquiridos distintos de la hemofilia A. Cualquier trastorno crónico o enfermedad importante que, en opinión del investigador, pueda poner en peligro la seguridad del paciente o el cumplimiento del protocolo. ?Incapacidad mental, falta de cooperación o barrera idiomática que impida una correcta comprensión y colaboración de los padres o los tutores legales del paciente. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Incidence of FVIII inhibitors |
Incidencia de inhibidores del FVIII |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
All objectives/endpoints will be evaluated when the first 50 PUP have reached at least 50 exposure dates, when the first 100 PUP have reached 100 exposure dates, and at end of trial. End of trial will be up to 4 years after the patient has reached 100 exposure dates. |
Todos los objetivos/criterios de valoración se evaluarán cuando los primeros 50 PNTP hayan alcanzado al menos 50 días de exposición, cuando los primeros 100 PNTP hayan alcanzado 100 días de exposición y al final del ensayo. El final del ensayo tendrá lugar 4 años como máximo después de que el paciente haya alcanzado 100 días de exposición. |
|
E.5.2 | Secondary end point(s) |
- Frequency of adverse events including serious adverse events and medical events of special interest. - Incidence of confirmed high titre inhibitors (defined as inhibitor titre > 5BU). - Number of breakthrough bleeding episodes during prophylaxis with N8-GP (annualised bleeding rate). - Haemostatic effect of N8-GP in treatment of bleeding episodes, assessed by a predefined 4-point haemostatic response scale ?excellent?, ?good?, ?moderate? and ?none?). |
?Frecuencia de acontecimientos adversos, incluidos los acontecimientos adversos graves y los acontecimientos médicos de interés especial. ?Incidencia de títulos elevados de inhibidores confirmados (lo que se define como un título de inhibidores > 5 UB). ?Número de episodios hemorrágicos intercurrentes durante la profilaxis con N8-GP (tasa anualizada de hemorragias). ?Efecto hemostático de N8-GP en el tratamiento de los episodios hemorrágicos, evaluado mediante una escala de respuesta hemostática de 4 puntos predefinida (?excelente?, ?bueno?, ?moderado? y ?nulo?). |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All objectives/endpoints will be evaluated when the first 50 PUP have reached at least 50 exposure dates, when the first 100 PUP have reached 100 exposure dates, and at end of trial. End of trial will be up to 4 years after the patient has reached 100 exposure dates. |
Todos los objetivos/criterios de valoración se evaluarán cuando los primeros 50 PNTP hayan alcanzado al menos 50 días de exposición, cuando los primeros 100 PNTP hayan alcanzado 100 días de exposición y al final del ensayo. El final del ensayo tendrá lugar 4 años como máximo después de que el paciente haya alcanzado 100 días de exposición. |
|
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 | 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 |
Immunogenicity |
Inmunogeneicidad |
|
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Canada |
China |
Japan |
European Union |
Algeria |
Argentina |
Australia |
Korea, Republic of |
Malaysia |
Thailand |
Israel |
Mexico |
Serbia |
Taiwan |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 12 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
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 | 12 |