E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Severe haemophilia A |
Hemofilia A grave |
|
E.1.1.1 | Medical condition in easily understood language |
Severe bleeding disorder |
Trastorno hemorrágico grave |
|
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 | 16.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10018938 |
E.1.2 | Term | Haemophilia 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 compare the annualized total bleeding rate of individually tailored prophylaxis with the historical bleeding rate observed in patients having received on-demand treatment with Human-cl rhFVIII from study GENA-01 |
Comparar la tasa total anual de hemorragias de la profilaxis individualizada con la tasa de hemorragias histórica observada en pacientes que han recibido tratamiento a demanda con factor Human-cl rhFVIII del ensayo GENA-01 |
|
E.2.2 | Secondary objectives of the trial |
1. To compare the annualized spontaneous bleeding rate of individually tailored prophylaxis with the historical bleeding rate observed in patients having received on-demand treatment with Human-cl rhFVIII 2. To compare the annualized total bleeding rate in patients with 2x/week (or less) prophylaxis with the historical bleeding rate observed in patients having received on demand treatment with Human-cl rhFVIII To assess: 3. Median prophylactic dosing interval 4. Human-cl rhFVIII consumption data 5. PK of Human-cl rhFVIII in terms of FVIII:C 6. Safety of Human-cl rhFVIII
Additional objectives: To assess: 1. Thrombin generation assay (TGA) in terms of its usefulness in individualizing therapy for patients on prophylaxis 2. Clinical efficacy of Human-cl rhFVIII in the treatment of breakthrough bleeding episodes (BEs) 3. Clinical efficacy of Human-cl rhFVIII in surgical prophylaxis 4. Correlation of vWF antigen concentration and half-life of Human-cl rhFVIII |
1.Comparar la tasa anual de hemorragias espontáneas de la profilaxis individualizada con la tasa de hemorragias histórica en pacientes que han recibido tratamiento a demanda con factor Human-cl rhFVIII 2.Comparar la tasa anual total de hemorragias en pacientes con profilaxis 2 veces/semana (o inferior) con la tasa de hemorragias histórica en pacientes que han recibido tratamiento a demanda con factor Human-cl rhFVIII Evaluar: 3.La mediana del intervalo de administración profiláctico 4.El consumo de Human-cl rhFVIII 5.La PK de Human-cl rhFVIII en términos de FVIII:C 6.La seguridad de Human-cl rhFVIII Obj. adicionales. Evaluar: 1.TGA según su utilidad en el tratamiento individualizado para los pacientes en la profilaxis 2.Eficacia clínica de Human-cl rhFVIII en el tratamiento de los episodios hemorrágicos repentinos 3.Eficacia clínica de Human-cl rhFVIII en profilaxis quirúrgica 4.Correlación de una concentración del antígeno del vWF y de la semivida de Human-cl rhFVIII |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
(a) Severe haemophilia A (FVIII:C < 1%) according to medical history (b) Male patients >= 18 years of age (c) Previous treatment with a FVIII concentrate (regular prophylaxis with good compliance or on-demand treatment) for at least 150 EDs (d) Good documentation regarding dosing and bleeding frequency in the 6 months preceding study start (e) Immunocompetence (CD4+ count > 200/microliter) (f) HIV-negative according to medical history; if positive, viral load < 200 particles/microliter or < 400,000 copies/mL (g) Freely given written informed consent |
(a) Hemofilia A grave (FVIII:C < 1%) según historia clínica (b) Pacientes varones >= 18 años de edad (c) Tratamiento previo con un concentrado de FVIII (profilaxis regular con buen cumplimiento o tratamiento a demanda) durante como mínimo 150 DE (d) Buena documentación con respecto a la administración y a la frecuencia de las hemorragias en los 6 meses anteriores al inicio del ensayo clínico (e) Inmunocompetencia (cifra CD4+ > 200/microlitro) (f) VIH negativo según historia clínica; si es positivo, carga viral < 200 partículas/microlitro o < 400.000 copias/mL (g) Consentimiento informado libremente otorgado por escrito |
|
E.4 | Principal exclusion criteria |
(a) Any coagulation disorder other than haemophilia A (b) Present or past FVIII inhibitor activity (>= 0.6 BU) according to medical history (c) Severe liver or kidney disease (ALT and AST levels > 5 times of upper limit of normal, creatinine > 120 micrmoles/L) (d) Treatment with any investigational medicinal product (IMP) except FVIII IMP within 14 days prior to the screening visit |
(a) Cualquier trastorno de coagulación distinto de la hemofilia A (b) Actividad con inhibidor del factor FVIII presente o pasada (? 0.6 UB) según historia clínica (c) Patología grave de hígado o riñón (niveles de ALT y AST > 5 veces el límite superior de lo normal, creatinina > 120 micromol/L) (d) Tratamiento con cualquier producto en investigación (PI) excepto PI de FVIII durante los 14 días previos a la visita de selección |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Reduction of the annualized total bleeding rate observed in the GENA-01 study (58.1 total bleeding episodes per patient per year) by 50% during individually tailored prophylaxis |
Reducción de la tasa total anual de hemorragias observada en el ensayo GENA-01 (58,1 episodios hemorrágicos totales por paciente y año) en un 50% durante la profilaxis individualizada |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At the end of the study |
Al final del estudio |
|
E.5.2 | Secondary end point(s) |
1. Reduction of the annualized spontaneous bleeding rate observed in the GENA-01 study (38.5 spontaneous bleeding episodes per patient per year) by 50% during individually tailored prophylaxis 2. Reduction of the annualized bleeding rate observed in GENA-01 by 50% in patients with 2x/week prophylaxis or less 3. Median prophylactic dosing interval during individually tailored prophylaxis 4. Human-cl rhFVIII consumption data (FVIII IU/kg per month per patient) during individually tailored prophylaxis 5. Safety and tolerability of Human-cl rhFVIII by monitoring adverse events (AEs) throughout the study |
1. Reducción de la tasa anual de hemorragias espontáneas observada en el ensayo GENA-01 (38,5 episodios hemorrágicos espontáneos por paciente y año) en un 50% durante la profilaxis individualizada 2. Reducción de la tasa anual de hemorragias observada en el GENA-01 en un 50% en pacientes con profilaxis 2 veces/semana o menos 3. Mediana del intervalo de administración profiláctico durante la profilaxis individualizada 4. Datos de consumo de human-cl rhFVIII (FVIII UI/kg al mes por paciente) durante la profilaxis individualizada 5. Seguridad y tolerabilidad de human-cl rhFVIII mediante la supervisión de los acontecimientos adversos (AA) durante todo el estudio. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be evaluated at the end of the study with the exception of the 5th secondary endpoint, Safety and tolerability of Human-cl rhFVIII by monitoring adverse events (AEs), which will take place throughout the study |
Todos los criterios de valoración secundarios se valorarán al final del estudio con la excepción del 5º criterio secundario, seguridad y tolerabilidad de human-cl rhFVIII mediante la supervisión de los acontecimientos adversos (AA), que se valorará durante todo el estudio. |
|
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 | 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 | Information not present in EudraCT |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Information not present in EudraCT |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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
| 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 | 27 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
LVLS |
Ultima visita del último paciente |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 15 |
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 | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |