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 del 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 immunogenicity of NNC 0129-0000-1003 (hereafter referred to as N8-GP) in previously treated patients with Haemophilia A - To evaluate the clinical efficacy of N8-GP in bleeding prophylaxis (number of bleeds during prophylaxis) |
- Evaluar la inmunogenicidad del NNC 0129-0000-1003 (en adelante N8-GP) en los pacientes con hemofilia A y tratamiento previo. -Evaluar la eficacia clínica del N8-GP para la profilaxis de la hemorragia (número de episodios hemorrágicos durante la profilaxis). |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the clinical efficacy of N8-GP when treating bleeds in patients with haemophilia A - To evaluate the safety of N8-GP when used for prevention of bleeds and treatment of bleeds in patients with haemophilia A - To evaluate PK properties of N8-GP - To evaluate Patient Reported Outcomes - To evaluate the health economic impact of N8-GP treatment - Generation of a population based PK-model for N8-GP |
- Evaluar la eficacia clínica del N8-GP para el tratamiento de las hemorragias en los pacientes con hemofilia A. -Evaluar la seguridad del N8-GP cuando se utiliza para la prevención de las hemorragias y el tratamiento de hemorragias en los pacientes con hemofilia A. -Evaluar las propiedades farmacocinéticas del N8-GP. -Evaluar los resultados comunicados por los pacientes. -Evaluar el efecto del tratamiento con N8-GP sobre la economía sanitaria. -Elaborar un modelo farmacocinético poblacional del N8-GP. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male patients with severe congenital haemophilia A (FVIII activity <1%, according to medical records) - Documented history of at least 150 EDs to other FVIII products - Age ? 12 years and body weight ? 35 kg (except for Croatia and The Netherlands where the lower age limit will be 18 years) |
-Varones con hemofilia A congénita grave (actividad del FVIII < 1% según la historia clínica). -Antecedentes documentados de al menos 150 DE a cualquier otro producto de FVIII. -Edad ? 12 años y peso corporal ?35 kg (salvo en Croacia y Países Bajos, donde el límite inferior de edad será de 18 años). |
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E.4 | Principal exclusion criteria |
- Previous participation in this trial defined as withdrawal after administration N8-GP - Any history of FVIII inhibitors - FVIII inhibitors ? 0.6 BU/mL at screening - HIV positive, defined by medical records with CD4+ count ?200/µL or a viral load of >400000 copies/mL If the data is not available in medical records within last 6 months, CD4+ will be measured at the screening visit - Congenital or acquired coagulation disorders other than haemophilia A - Previous significant thromboembolic events (e.g. myocardial infarction, cerebrovascular disease or deep venous thrombosis) as defined by available medical records - Platelet count < 50,000 platelets/µL (laboratory value at the screening visit) - ALAT > 3 times the upper limit of normal reference ranges at central laboratory - Creatinine level ? 1.5 times above upper normal limit (according to central laboratory reference ranges) - Ongoing immune modulating or chemotherapeutic medication |
- Participación previa en este ensayo, definida como la retirada tras la administración de N8-GP. - Antecedentes de inhibidores del FVIII - Título de inhibidores del FVIII ? 0,6 UB/ml en el momento de la selección. - Infección por el VIH, definida por un recuento de linfocitos CD4+ ? 200/ µl o una carga viral > 400.000 copias/ml recogidos en la historia clínica. En caso de que la historia clínica no contenga estos datos correspondientes a los últimos 6 meses, se medirá el recuento de linfocitos CD4+ en la visita de selección. - Trastornos de la coagulación congénitos o adquiridos distintos de la hemofilia A. - Antecedentes de episodios tromboembólicos de importancia clínica (por ejemplo, infarto de miocardio, enfermedad cerebrovascular o trombosis venosa profunda) recogidos en la historia clínica. - Recuento de plaquetas < 50.000 /µl (valor analítico en la visita de selección). - ALAT > 3 veces el límite superior del intervalo de referencia de la normalidad del laboratorio central. - Valor de creatinina ? 1,5 veces el límite superior de la normalidad (según los intervalos de referencia del laboratorio central). - Tratamiento en curso con inmunomoduladores o quimioterápicos. |
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E.5 End points |
E.5.1 | Primary end point(s) |
- The Incidence rate of FVIII-inhibitors ?0.6 BU - Annualised bleeding rate in the prophylaxis arm |
- Incidencia de un título de inhibidores del FVIII ? 0,6 UB. - Tasa anualizada de hemorragias en el grupo de profilaxis. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
The endpoints will be analysed based on all available information until the end of trial (EOT) visit and up to approximately 19 months. |
Las variables se analizarán basándose en toda la información disponible hasta el final del ensayo (FE), es decir, hasta aproximadamente 19 meses. |
|
E.5.2 | Secondary end point(s) |
- Haemostatic effect of N8-GP when used for treatment of bleeds, assessed on a four-point scale for haemostatic response (excellent, good, moderate and none) by counting excellent and good as success and moderate and none as failure. |
- Efecto hemostático del N8-GP cuando se utiliza para el tratamiento de las hemorragias, evaluado en una escala de cuatro puntos según la respuesta hemostática (excelente, buena, moderada o nula) y contando como éxitos las respuestas excelentes y buenas y como fracasos las respuestas moderadas o nulas |
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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 the end of trial (EOT) visit and up to approximately 19 months. |
Las variables se analizarán basándose en toda la información disponible hasta el final del ensayo (FE), es decir, hasta aproximadamente 19 meses. |
|
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 | 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) | 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 | 8 |
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 | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |