E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hemophilia A with Inhibitors |
Hemofilia A con Inhibidores |
|
E.1.1.1 | Medical condition in easily understood language |
Hemophilia A is a genetic deficiency in blood clotting factor VIII, which causes increased bleeding. Inhibitors, however, prevent replacement factor VIII concentrates from controlling bleeds. |
La Hemofilia A es una deficiencia genetica en el factor VIII de cogulación que produce un aumento del sangrado. Los inhibidores impiden el reemplazo de los concentrados de factor VIII. |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10060612 |
E.1.2 | Term | Hemophilia A |
E.1.2 | System Organ Class | 100000004850 |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
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.1.3 | 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 efficacy of prophylactic RO5534262 compared with no prophylaxis in patients with hemophilia A with inhibitors |
Evaluar la eficacia de RO5534262 profiláctico en comparación con la no profilaxis en pacientes con hemofilia A con inhibidores |
|
E.2.2 | Secondary objectives of the trial |
? To evaluate - reduction in the number of bleeds - reduction in the number of joint bleeds and target joint bleeds - health-related quality of life - health status ? To evaluate the overall safety of prophylactic RO5534262 ? To characterize the exposure of prophylactic RO5534262 |
? Evaluar: -La reducción en el número de hemorragias -La reducción en el número de hemorragias articulares y hemorragias en las articulaciones diana -La calidad de vida relacionada con la salud - El estado de salud ? Evaluar la seguridad global de RO5534262 profiláctico ? Caracterizar la exposición a RO5534262 profiláctico |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Aged 12 years or older at the time of informed consent - Body weight >= 40 kg at the time of screening - Diagnosis of congenital hemophilia A of any severity and documented history of high-titer inhibitor (i.e., >= 5 Bethesda Units) - Documentation of treatment with episodic or prophylactic bypassing agents for at least the last 24 weeks - Adequate hematologic function - Adequate hepatic function - Adequate renal function - For women who are not postmenopausal or surgically sterile: agreement to remain abstinent or use single or combined highly effective non-hormonal contraceptive methods |
-Edad de 12 años o más en el momento del consentimiento informado -Peso corporal >= 40 kg en el momento de la selección -Diagnóstico de hemofilia A congénita de cualquier grado y antecedentes documentados de título alto de inhibidores (es decir, >=5 Unidades Bethesda [UB]) -Documentación del tratamiento a demanda o profiláctico con agentes by-pass durante al menos las 24 últimas semanas. -Función hematológica adecuada -Función hepática adecuada -Función renal adecuada -Para mujeres no posmenopáusicas o no sometidas a esterilización quirúrgica: acuerdo para mantener la abstinencia o para utilizar métodos anticonceptivos no hormonales de alta eficacia individuales o combinados |
|
E.4 | Principal exclusion criteria |
- Inherited or acquired bleeding disorder other than hemophilia A - Ongoing (or plan to receive during the study) immune tolerance induction therapy or prophylaxis with FVIII - History of illicit drug or alcohol abuse within 48 weeks prior to screening, in the investigator?s judgment - Previous or current treatment for thromboembolic disease (with the exception of previous catheter-associated thrombosis for which antithrombotic treatment is not currently ongoing) or signs of thromboembolic disease - Previous or concurrent autoimmune or connective tissue disease - History of hypersensitivity associated with monoclonal antibody therapies or components of the RO5534262 injection - Known HIV infection with CD4 count < 200 cells/microliter within 24 weeks prior to screening - Use of systemic immunomodulators (e.g., interferon or rituximab) at enrollment or planned use during the study, with the exception of antiretroviral therapy - Concurrent disease, treatment, or abnormality in clinical laboratory tests that could interfere with the conduct of the study or that would, in the opinion of the investigator or Sponsor, preclude the patient?s safe participation in and completion of the study or interpretation of the study results - Planned surgery (excluding minor procedures such as tooth extraction or incision and drainage) during the study - Receipt of ? RO5534262 in a prior investigational study ? An investigational drug to treat or reduce the risk of hemophilic bleeds within 5 half-lives of last drug administration ? A non-hemophilia-related investigational drug within last 30 days or 5 half lives, whichever is shorter ? An investigational drug concurrently - Unwillingness to use highly effective contraception methods for the specified duration in the protocol (females only, unless required otherwise by the local health authority) - Clinically significant abnormality on screening evaluations or laboratory tests that, in the opinion of the investigator, may pose an additional risk in administering study drug to the patient - Pregnancy or lactation, or intent to become pregnant during the study |
-Trastorno hemorrágico hereditario o adquirido distinto de la hemofilia A -Tratamiento de inducción de inmunotolerancia o profilaxis con FVIII en curso (o previsto durante el estudio) -Antecedentes de drogadicción o alcoholismo en las 48 semanas previas a la selección, según el criterio del investigador -Tratamiento previo o concomitante para enfermedad tromboembólica (con la excepción de la trombosis previa asociada al catéter que no esté siendo tratada con anti-trombóticos) o signos de enfermedad tromboembólica -Enfermedad autoinmune o de los tejidos conjuntivos previa o concomitante -Antecedentes de hipersensibilidad relacionada con terapias con anticuerpos monoclonales o con componentes de la inyección de RO5534262 -Infección conocida por VIH con recuento de CD4 < 200 células/microlitro en las 24 semanas previas a la selección -Uso de inmunomoduladores sistémicos (por ejemplo, interferón o rituximab) en el momento de la inclusión en el estudio o uso previsto durante el estudio, a excepción de la terapia antirretroviral -Enfermedad, tratamiento o anomalía concurrente en los análisis clínicos que pudiera interferir con la realización del estudio o que, en opinión del investigador o del Promotor, impediría la participación segura del paciente en el estudio y la finalización del estudio o la interpretación de los resultados del mismo. -Intervención prevista (excepto intervenciones menores como extracciones dentales o incisiones y drenajes) durante el estudio -Recepción de: ?RO5534262 en un estudio de investigación previo ?Un fármaco de investigación para tratar o reducir el riesgo de sangrados hemofílicos durante 5 semividas del fármaco del estudio ?un fármaco de investigación no relacionado con la hemofilia en los últimos 30 días o 5 semividas, aquello que sea menor ?un fármaco de investigación concurrente -Renuncia a utilizar métodos anticonceptivos de alta eficacia durante el periodo de tiempo especificado en el protocolo (sólo para mujeres, a menos que las autoridades sanitarias locales establezcan lo contrario) -Anomalía clínicamente significativa en las evaluaciones o en las pruebas analíticas realizadas durante la selección que, en opinión del investigador, pueda suponer un riesgo adicional a la administración del fármaco del estudio al paciente -Embarazo o lactancia, o intento de quedarse embarazada durante el estudio |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Number of bleeds over time |
Número de hemorragias a lo largo del tiempo |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Over 24 weeks or discontinuation of study participation, whichever occurs first |
Mas de 24 semanas o discontinuación de la participación en el estudio, lo que ocurra antes |
|
E.5.2 | Secondary end point(s) |
1. Number of bleeds over time 2. Number of joint bleeds over time 3. Number of target joint bleeds over time 4. Quality of Life questionnaires 5. Health status questionnaire 6. Incidence and severity of adverse events 7. Incidence of thromboembolic events 8. Incidence of adverse events leading to drug discontinuation 9. Incidence of severe hypersensitivity, anaphylaxis, and anaphylactoid events 10. Incidence of anti-RO5534262 antibodies 11. Plasma concentrations of RO5534262 |
1- Numero de hemorragias a lo largo el tiempo 2- Numero de hemorragias articulares a lo largo del tiempo 3-Numero de hemorragias en las articulaciones diana a lo largo del tiempo 4- Cuestionarios de calidad de vida 5-Cuestionarios de estado de salud 6-Incidencia e intensidad de los acontecimientos adversos 7-Incidencia de los acontecimientos tromboembólicos 8-Incidencia de los acontecimientos adversos que provocan la interrupción del fármaco 9-Incidencia de acontecimientos de hipersensibilidad severa, anafilaxia y acontecimientos anafilactoides 10-Incidencia de los anticuerpos anti-RO5534262 11-Concentraciones plasmáticas de RO5534262 |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3. Over 24 weeks or discontinuation of study participation, whichever occurs first 4-5. At Weeks 24 and 48 6-10. Up to the end of the study (estimated to be approximately 108 weeks after the first enrolled patient) 11. Upon starting RO5534262 ? Every week during Weeks 1?4 ? Every 2 weeks during Weeks 5?8 ? Every 4 weeks during Weeks 9?24 ? Every 8 weeks during Weeks 25?48 ? Every 12 weeks thereafter while on RO5534262, until the end of the study |
1-3. Mas de 24 semanas o discontinuación de la participación en el estudio, lo que ocurra antes 4-5. En las semanas 24 y 48 6-10. Como máximo hasta el final del estudio (estimado aproximadamente a las 108 semanas después de la inclusion del primer paciente) 11-En el momento de empezar con RO5534262 ?Cada semana durante las Semanas 1-4 ?Cada 2 semanas durante las Semanas 5-8 ?Cada 4 semanas durante las Semanas 9-24 ?Cada 8 semanas durante las Semanas 25-48 ?Cada 12 semanas a partir de entonces mientras se mantenga el tratamiento con RO5534262 y hasta el final del 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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
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 | 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 | Yes |
E.8.2.3.1 | Comparator description |
armB: no prophylaxis; armC: historical intrapatient control |
|
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 19 |
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 |
Germany |
Italy |
Japan |
Korea, Republic of |
Poland |
Spain |
Taiwan |
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
|
The end of this study is defined as the date when the last patient completes the end of study, safety follow-up visit 24 weeks after discontinuing RO5534262, enrolls in an RO5534262 extension study, or is lost to follow-up. |
El final de este estudio se define como la fecha en la que el último paciente completa el final del estudio, la visita de seguimiento 24 semanas después de interrumpir el tratamiento con RO5534262, se incluye en un estudio de ampliación de RO5534262 o se pierde durante el seguimiento. |
|
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 | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 1 |
E.8.9.2 | In all countries concerned by the trial days | 0 |