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 con Inhibidores |
|
E.1.1.1 | Medical condition in easily understood language |
Bleeding disorder, inherited deficiency in clotting factor VIII or factor IX with antibodies to clotting factor replacement therapy |
Trastorno hemorrágico, deficiencia hereditaria del factor VIII o del factor IX de coagulación con anticuerpos a 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 | 100000011928 |
|
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 | 100000011929 |
|
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 assess the efficacy of concizumab administered s.c. once daily in preventing bleeding episodes in haemophilia A and B patients with inhibitors |
Evaluar la eficacia de concizumab administrado s.c. una vez al día para prevenir los episodios hemorrágicos en pacientes con hemofilia A y B e inhibidores |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the longer-term efficacy of concizumab in haemophilia patients with inhibitors 2. To assess the safety of concizumab in haemophilia patients with inhibitors 3. To assess the safety of administering recombinant factor VIIa (rFVIIa) to haemophilia patients with inhibitors that are exposed to concizumab 4. To assess the immunogenicity of concizumab in haemophilia patients with inhibitors |
1. Evaluar la eficacia a largo plazo de concizumab en pacientes con hemofilia e inhibidores. 2. Evaluar la seguridad de concizumab en pacientes con hemofilia e inhibidores. 3. Evaluar la seguridad de la administración de factor VIIa recombinante (rFVIIa) en pacientes con hemofilia e inhibidores que están recibiendo concizumab. 4. Evaluar la inmunogenicidad de concizumab en pacientes con hemofilia 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 the suitability for the trial - Male haemophilia A or B patients with inhibitors aged 18 years or older at the time of signing informed consent - Patients currently in need of treatment with bypassing agents |
-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 realizados como parte del mismo, incluidas las actividades para determinar la idoneidad para participar en el ensayo. -Pacientes varones con hemofilia A o B e inhibidores, de 18 años o más de edad en el momento de firmar el consentimiento informado. -Pacientes con necesidad presente de tratamiento con agentes bypass. |
|
E.4 | Principal exclusion criteria |
- Known or suspected hypersensitivity to trial product(s) or related products - Known inherited or acquired bleeding disorder other than haemophilia - Ongoing or planned immune tolerance induction therapy or prophylaxis with FVIII or FIX |
-Confirmación o sospecha de hipersensibilidad a los productos del ensayo o a otros productos relacionados. -Trastorno hemorrágico hereditario o adquirido conocido distinto de la hemofilia. -Terapia de inducción de inmunotolerancia o profilaxis con FVIII o FIX en curso o previstas. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
The number of bleeding episodes |
El número de episodios hemorrágicos |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
During at least 24 weeks from treatment onset |
Durante 24 semanas, como mínimo, desde el comienzo del tratamiento |
|
E.5.2 | Secondary end point(s) |
1. The number of spontaneous bleeding episodes 2. Number of treatment emergent adverse events (TEAEs) |
1. El número de episodios hemorrágicos espontáneos 2. Número de acontecimientos adversos de aparición durante el tratamiento (TEAE) |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.+ 2. During at least 24 weeks from treatment onset
All endpoints referring to the time frame of at least 24 weeks will be evaluated in the main part of the trial, defined to end when the last patient has completed a minimum of 24 weeks of dosing treatment with trial product (or has withdrawn). In addition, number of bleeding episodes during 76 weeks of treatment with prophylactic concizumab will be analysed. |
1.*2. Durante 24 semanas, como mínimo, desde el comienzo del tratamiento.
Todos los criterios de valoración que hacen referencia al plazo de 24 semanas, como mínimo, se evaluarán en la parte principal del ensayo, cuyo final se ha definido cuando el último paciente haya completado un mínimo de 24 semanas de administración del tratamiento con el producto del ensayo (o se haya retirado). Además, se analizará el número de episodios hemorrágicos durante 76 semanas de tratamiento en profilaxis con concizumab. |
|
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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 |
Con escalada de dosis potencial |
With potential dose escalation |
|
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
European Union |
Israel |
Japan |
Malaysia |
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 | 2 |
E.8.9.1 | In the Member State concerned months | 5 |
E.8.9.1 | In the Member State concerned days | 7 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 7 |