E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Haemophilia A with inhibitors Haemophilia B with inhibitors |
Hemofilia A con inhibidores Hemofilia B sin inhibidores |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding disorders: - inherited deficiency in clotting factor VIII with antibodies to replacement therapy - inherited deficiency in clotting factor IX with antibodies to replacement therapy |
Trastornos hemorrágicos: deficiencia hereditaria del factor VIII y del factor IX de coagulación con anticuerpos para la terapia de reemplazo |
|
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 | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053751 |
E.1.2 | Term | Hemophilia A with anti factor VIII |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10053752 |
E.1.2 | Term | Hemophilia B with anti factor IX |
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 compare effect of concizumab prophylaxis to no prophylaxis (on-demand treatment with bypassing agents) in reducing the number of bleeding episodes in adult and adolescent patients with haemophilia A or B with inhibitors |
1. Comparar el efecto de la profilaxis con concizumab con el de la ausencia de profilaxis (tratamiento a demanda con agentes bypass) en lo que respecta a reducir el número de episodios hemorrágicos en pacientes adultos y adolescentes con hemofilia A o B e inhibidores. |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the patient reported outcomes (PROs) after treatment with concizumab prophylaxis vs no prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors 2. To investigate the safety of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors 3. To investigate the PK and PD parameters of concizumab prophylaxis in adult and adolescent patients with haemophilia A or B with inhibitors |
1. Comparar los resultados comunicados por los pacientes (RCP) después del tratamiento profiláctico con concizumab respecto a la ausencia de profilaxis en pacientes adultos y adolescentes con hemofilia A o B e inhibidores. 2. Investigar la seguridad de la profilaxis con concizumab en pacientes adultos y adolescentes con hemofilia A o B e inhibidores. 3. Investigar los parámetros farmacocinéticos y farmacodinámicos de la profilaxis con concizumab en pacientes adultos y adolescentes con hemofilia A o B e inhibidores. |
|
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 aged 12 or older years at the time of signing informed consent - Congenital Haemophilia A or B of any severity with documented history of inhibitor (0.6 BU or more) - Patient has been prescribed, or in need of, treatment with bypassing agents in the last 24 weeks prior to screening (for patients not previously enrolled in NN7415-4310) |
- Obtención del consentimiento informado antes de realizar ninguna de las actividades relacionadas 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 ensayo. - Varón de 12 años o más de edad en el momento de firmar el consentimiento informado. - Hemofilia A o B congénita de cualquier gravedad con antecedentes documentados de inhibidores (≥ 0,6 UB). - Prescripción o necesidad de tratamiento con agentes bypass en las 24 semanas previas a la selección (para los pacientes no incluidos previamente en el estudio NN7415-4310). |
|
E.4 | Principal exclusion criteria |
- Known or suspected hypersensitivity to monoclonal antibodies - Known inherited or acquired coagulation disorder other than congenital haemophilia - Ongoing or planned Immune Tolerance Induction treatment |
- Hipersensibilidad conocida o sospechada a anticuerpos monoclonales. - Trastorno de la coagulación hereditario o adquirido conocido distinto de hemofilia congénita. - Tratamiento de inducción de inmunotolerancia en curso o previsto. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of treated bleeding episodes (spontaneous and traumatic) |
Número de episodios hemorrágicos tratados (espontáneos y traumáticos) |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
From start of treatment (week 0) to the end of the main part (week 24) |
Desde el comienzo del tratamiento (semana 0) hasta el final de la parte principal (semana 24). |
|
E.5.2 | Secondary end point(s) |
1. Change in SF36v2 bodily pain 2. Change in SF36v2 physical functioning |
1. Variación del dolor corporal en el cuestionario SF36v2 2. Variación de la función física en el cuestionario SF36v2 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-2. From baseline (week 0) to week 24 |
1-2. Desde el momento basal (semana 0) hasta la semana 24. |
|
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 | Yes |
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 | 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 | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
2 randomised treatment arms (ppx/no ppx) and two non-randomised treatment arms |
|
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 | Yes |
E.8.2.3.1 | Comparator description |
Treatment regimen before entering the trial will determine the assignment to the four treatment arms |
|
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 59 |
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 |
Algeria |
Australia |
Canada |
European Union |
India |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Norway |
Russian Federation |
Serbia |
South Africa |
Turkey |
Ukraine |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
E.8.9.1 | In the Member State concerned months | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |