E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Congenital hemophilia A |
Hemofilia A congénita |
|
E.1.1.1 | Medical condition in easily understood language |
Hemophilia A is a rare but serious bleeding disorder which affects males and is characterized by a deficiency in the plasma protein known as coagulation Factor VIII. |
La hemofilia A es una alteración rara pero grave de la coagulación que afecta a varones y se caracteriza por una deficiencia de una proteína plasmática que se conoce como Factor VIII. |
|
E.1.1.2 | Therapeutic area | Body processes [G] - Genetic Phenomena [G05] |
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 | 10060613 |
E.1.2 | Term | Hemophilia A (Factor VIII) |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of rVIII-SingleChain in the treatment of major and minor bleeding events based on the investigator?s 4-point assessment scale. |
Evaluar la eficacia de rVIII-Cadena Simple en el tratamiento de hemorragias mayores y menores en base a una escala de valoración de 4 puntos. |
|
E.2.2 | Secondary objectives of the trial |
- To evaluate the annualized bleeding rate during prophylaxis treatment - To evaluate the annualized bleeding rate during on-demand treatment - To evaluate the proportion of bleeding episodes requiring 1, 2, 3, or >3 infusions of rVIII-SingleChain to achieve hemostasis - To evaluate the consumption of rVIII-SingleChain - To evaluate the pharmacokinetic (PK) profile of rVIII-SingleChain - To assess the rate of inhibitor formation to rVIII-SingleChain - To assess the safety of rVIII-SingleChain with regard to adverse events (AEs), laboratory parameters, physical examination, and vital signs (blood pressure, heart rate, temperature, and respiratory rate) |
- Evaluar el índice de hemorragia anualizado durante el tratamiento profiláctico. - Evaluar el índice de hemorragia anualizado durante el tratamiento a demanda. - Evaluar la proporción de episodios hemorrágicos requiriendo 1, 2, 2, o >3 infusiones de rVIII-CadenaSimple para alcanzar la hemostasia. - Evaluar el consumo de rVIII-CadenaSimple - Evaluar el perfil farmacocinético (FC) de rVIII-CadenaSimple - Valorar la tasa de formación de inhibidores para rVIII-CadenaSimple - Valorar la seguridad de rVIII-CadenaSimple en relación a acontecimientos adversos (AAs), parámetros de laboratorio, examen físico y constantes vitales (tensión arterial, frecuencia cardiaca, temperatura y frecuencia respiratoria) |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of severe hemophilia A defined as < 1% Factor VIII (FVIII) concentration (FVIII:C) documented in medical records, - Males < 12 years of age, - Subjects who have received > 50 EDs with a FVIII product, - Prior PK data (at least incremental recovery and half-life) from previous FVIII exposure for subjects participating in the PK part - Investigator believes that the subject is willing and able to adhere to all protocol requirements. Investigator believes that the subject?s parent(s) or legally acceptable representative(s) is / are willing and able to adhere to all protocol requirements. |
- Diagnóstico de hemofilia A grave definido como una concentración de FVIII (FVIII:C) < 1% documentada en la historia clínica, - Varones < 12 años de edad, - Sujetos que hayan recibido > 50 DEs con un producto FVIII, - Datos anteriores de FC (al menos recuperación incremental y vida media) de exposición previa a FVIII para sujetos participantes en la parte FC, - El investigador cree que el sujeto está dispuesto y es capaz de cumplir con todos los requerimientos del protocolo. El investigador cree que los padres del sujeto o representantes legales están dispuestos y son capaces de cumplir con todos los requerimientos del protocolo. |
|
E.4 | Principal exclusion criteria |
- Any history of or current FVIII inhibitors - Use of an Investigational Medical Product (IMP) within 30 days prior to the first rVIII-SingleChain administration, - Administration of any cryoprecipitate, whole blood or plasma within 30 days prior to administration of rVIII-SingleChain, - Known hypersensitivity (allergic reaction or anaphylaxis) to any FVIII product or hamster protein, ? Subject currently receiving IV immunomodulating agents such as immunoglobulin or chronic systemic corticosteroid treatment, ? Subject with serum aspartate aminotransferase (AST) or serum alanine aminotransferase (ALT) values >5 times (x) the upper limit of normal (ULN) at Screening, ? Subjects with serum creatinine values >2 x ULN at Screening, ? Evidence of thrombosis, including deep vein thrombosis, stroke, pulmonary embolism, myocardial infarction and arterial embolus within 3 months before Day 1, ? Experienced life-threatening bleeding episode or had major surgery or an orthopedic surgical procedure during the 3 months before rVIII-SingleChain administration. |
- Antecedentes o presencia de inhibidores de FVIII, - Utilización de un medicamento en investigación (IMP) en los 30 días anteriores a la primera administración de rVIII-CadenaSimple, - Administración de cualquier crioprecipitado, sangre entera o plasma en los 30 días anteriores a la administración de rVIII-CadenaSimple, - Hipersensibilidad conocida (reacción alérgica o anafilaxis) a cualquier producto FVIII o a la proteína de hámster, - Sujetos recibiendo actualmente agentes inmunomoduladores IV tales como inmunoglobulinas o tratamiento crónico sistémico con corticosteroides, - Sujetos con valores séricos de aspartato aminotransferasa (AST) o de alanino aminotransferasa (ALT) >5 veces (x) el límite superior normal (LSN) en la Selección, - Sujetos con valores de creatinina sérica >2 x LSN en la Selección, - Evidencia de trombosis, incluido trombosis venosa profunda, embolia cerebral, embolia pulmonar, infarto de miocardio y embolia arterial en los 3 meses anteriores al Día 1, - Haber sufrido un episodio hemorrágico potencialmente mortal o haberse sometido a cirugía mayor o cirugía ortopédica en los 3 meses anteriores a la administración de rVIII-CadenaSimple. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Treatment success |
Éxito del tratamiento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Up to two years |
Hasta dos años |
|
E.5.2 | Secondary end point(s) |
- Annualized bleeding rate - Proportion of bleeding episodes requiring 1, 2, 3, or more than 3 infusions of rVIII-SingleChain to achieve hemostasis. - Consumption of rVIII-SingleChain - The number of subjects with inhibitor formation to rVIII-SingleChain
PK: - Incremental recovery - Half-life (t1/2) of rVIII-SingleChain - Area under the concentration curve (AUC) - Clearance (Cl) of rVIII-SingleChain |
- Índice de hemorragia anualizado - Proporción de episodios hemorrágicos requiriendo1, 2, 3, o más de 3 infusiones de rVIII-CadenaSimple para alcanzar la hemostasia. - Consumo de rVIII-CadenaSimple - Número de sujetos con formación de inhibidores a rVIII-CadenaSimple
FC: - Recuperación incremental - Vida media (t1/2) de rVIII-CadenaSimple - Área bajo la curva de concentración (AUC) - Aclaramiento (Cl) de rVIII-CadenaSimple |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Up to two years; for PK endpoints, 0 to 2 days after infusion. |
Hasta dos años; para las variables de FC, 0 a 2 días después de la infusión. |
|
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 | Yes |
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 | Yes |
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) | Information not present in EudraCT |
E.8.2.2 | Placebo | Information not present in EudraCT |
E.8.2.3 | Other | Information not present in EudraCT |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Chile |
Philippines |
Korea, Democratic People's Republic of |
Malaysia |
Russian Federation |
Ukraine |
South Africa |
Switzerland |
Thailand |
Turkey |
United States |
European Union |
Georgia |
|
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
|
LVLS |
Última visita del último sujeto |
|
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 | 4 |
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 | 4 |
E.8.9.2 | In all countries concerned by the trial days | 0 |