E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A |
Hemofilia A |
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E.1.1.1 | Medical condition in easily understood language |
Bleeding disorder type A |
Trastorno hemorrágico: Deficiencia de Factor VIII. |
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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 | 10018937 |
E.1.2 | Term | Haemophilia A |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 |
To evaluate the haemostatic effect of N8-GP during surgical procedures in patients with haemophilia A |
Evaluar el efecto hemostático de N8-GP durante procedimientos quirúrgicos en pacientes con hemofilia A. |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the general safety including immunogenicity of N8-GP when used for prevention and treatment of bleeding throughout the surgical period - To evaluate the haemostatic effect of N8-GP during the post-operative period - To evaluate health economic resource use (hospitalisation days) due to surgery |
- Evaluar la seguridad general, incluida la inmunogenicidad, de N8-GP cuando se utiliza en la prevención y el tratamiento de las hemorragias durante el período quirúrgico. - Evaluar el efecto hemostático de N8-GP durante el posoperatorio. - Evaluar la utilización de recursos de economía sanitaria (días de hospitalización) como consecuencia de la cirugía. |
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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 procedure that would not have been performed during normal management of the subject.) - Ongoing participation in the pathfinderTM 2 (NN7088-3859) or the pathfinderTM 4 (NN7088-3861) trial and having received ?5 doses of N8-GP - Undergoing major surgery (refer to Section 5.3.1 for definition) requiring daily monitoring of FVIII:C and wound status for ?3 days - The patient and/or Legally Acceptable Representative (LAR) is capable of assessing a bleeding episode, keeping an eDiary, capable of home treatment of bleeding episodes and otherwise capable of following the trial procedures |
- Obtención del consentimiento informado antes de realizar ninguna actividad relacionada con el ensayo. (Se consideran actividades relacionadas con el estudio todos los procedimientos que no se llevarían a cabo como parte del tratamiento normal del sujeto.) - Participación en curso en pathfinderTM 2 (NN7088-3859) o pathfinderTM 4 (NN7088-3861) y haber recibido ?5 dosis de N8-GP. - Someterse a una intervención de cirugía mayor (véase la definición en el apartado 5.3.1 ) que exija vigilancia diaria del FVIII:C y del estado de la herida durante 3 días o más. - El paciente o su representante legal (RL) es capaz de evaluar un episodio hemorrágico, de llevar un diario electrónico, de tratar los episodios hemorrágicos en su casa y, en general, de cumplir los procedimientos del estudio. |
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E.4 | Principal exclusion criteria |
- Known or suspected hypersensitivity to trial product including allergy to hamster protein or related products - Previous withdrawal from the pathfinderTM 2 (NN7088-3859) or the pathfinderTM 4 (NN7088-3861) trial after administration of trial product, except interruption due to inclusion in this pathfinderTM 3 trial (NN7088-3860) - The receipt of any investigational medicinal product (except N8-GP) within 30 days prior to enrolment into the trial. (For Brazil, only: Participation in a previous clinical trial within one year prior to screening for this trial (Visit 1), unless there is a direct benefit to the research subject, at the Investigator?s discretion) - FVIII inhibitors ? 0.6 BU/mL at screening (refer to Section 8.1.1) - Previous arterial thrombotic events (e.g. myocardial infarction and intracranial thrombosis) or previous deep venous thrombosis or pulmonary embolism (as defined by available medical records) - Immune modulating or chemotherapeutic medication - Any disease (liver, kidney, inflammatory and mental disorders included) or condition which, according to the Investigator?s judgement, could imply a potential hazard to the patient, interfere with trial participation or trial outcome - Unwillingness, language or other barriers precluding adequate understanding and/or cooperation |
- Hipersensibilidad confirmada o presunta al producto del ensayo, como alergia a las proteínas de hámster o a otros productos relacionados. - Retirada anterior de pathfinderTM 2 (NN7088-3859) o pathfinderTM 4 (NN7088-3861) después de la administración del producto del ensayo, salvo que la interrupción se deba a la inclusión en este ensayo pathfinderTM 3 (NN7088-3860). - Haber recibido algún medicamento en investigación (excepto N8-GP) en los 30 días previos a la inclusión en el estudio. (Sólo en Brasil: haber participado en un ensayo clínico durante el año anterior a la visita de selección (visita 1), a menos que exista un beneficio directo para el sujeto de la investigación a criterio del investigador. - Inhibidores de FVIII ?0,6 UB/ml en la selección (véase el apartado 8.1.1). - Acontecimientos trombóticos arteriales anteriores (por ejemplo, infarto de miocardio y trombosis intracraneal) o trombosis venosa profunda o embolia pulmonar (según los registros médicos disponibles). - Recibir medicamentos inmunomoduladores o quimioterápicos. - Cualquier enfermedad o trastorno (incluidos los hepáticos, renales, inflamatorios y mentales) que, según el criterio del investigador, pudiera entrañar un peligro para el paciente o interferir en la participación en el ensayo o en su resultado. - Falta de voluntad o barreras idiomáticas o de otro tipo que impidan el entendimiento adecuado o la colaboración. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Haemostatic effect during surgery evaluated by the four-point scale, assessed by the Investigator/surgeon at the day of surgery - Four-point response scale: excellent, good, moderate or none |
- Efecto hemostático durante la cirugía en una escala de cuatro puntos evaluada por el investigador/cirujano el día de la intervención. - Escala de respuesta de cuatro puntos: excelente, buena, moderada o nula. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
During surgery |
Durante la cirugía |
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E.5.2 | Secondary end point(s) |
- Average consumption of N8-GP during surgery - Haemostatic effect of N8-GP during the post-operative period Days 1-6 and 7-14 - Average consumption of N8-GP during the post-operative period Days 1-6 - Incidence rate of inhibitors against factor VIII (FVIII) (?0.6 BU/mL) |
- Consumo medio de N8-GP durante la cirugía. - Efecto hemostático de N8-GP durante el período postoperatorio, días 1-6 y 7-14. - Consumo medio de N8-GP durante los días del postoperatorio 1-6. - Incidencia de inhibidores del factor VIII (FVIII) (?0,6 UB/ml) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be analysed based on all available information until End of Trial (EOT) Visit and up to approximately 5 weeks for each patient. |
Las variables se analizarán basándose en toda la información disponible hasta el final del ensayo, es decir, hasta aproximadamente 5 semanas por paciente. |
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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 | No |
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 | 30 |
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 |
Croatia |
Denmark |
France |
Germany |
Hungary |
Italy |
Japan |
Korea, Republic of |
Malaysia |
Netherlands |
Norway |
Russian Federation |
Spain |
Sweden |
Switzerland |
Taiwan |
Turkey |
United Kingdom |
United States |
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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
|
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 5 |
E.8.9.2 | In all countries concerned by the trial days | 0 |