E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with life-threatening HES |
Sujetos con síndrome hipereosinofílico (HES) severo o potencialmente mortal |
|
E.1.1.1 | Medical condition in easily understood language |
Subjects with HES |
Sujetos con HES |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048643 |
E.1.2 | Term | Hypereosinophilic syndrome |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
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 |
Safety:
To assess the long-term AE profile associated with mepolizumab therapy.
Efficacy:
To characterize individual dosing requirements for control of disease. |
Seguridad:
Evaluar los AA a largo plazo asociados con mepolizumab.
Eficacia:
Caracterizar los requerimientos de la dosis individual para controlar la enfermedad. |
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E.2.2 | Secondary objectives of the trial |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. In accordance with local procedures, written informed consent/assent can be obtained from the subject or legally authorized representative
2. ≥ 12 years of age at the time of signing the informed consent/assent
3. Meets the diagnostic criteria for HES as defined by:
- Eosinophilia >1500 cells/μl for at least 6 months with evidence of symptoms and signs of organ system involvement or dysfunction that can be directly related to eosinophilia (with no evidence of parasitic, allergic or other recognized causes of eosinophilia such as connective tissues disease, malignancy) or
- Eosinophilia of >1500 cells/μl for less than 6 months and meet the other criteria for HES accompanied by clear evidence of eosinophil tissue infiltration and with exclusion of secondary causes of eosinophilia as above.
4. Subjects meeting all three of the following criteria will be eligible:
- The indication, HES, is a seriously debilitating or life-threatening disease;
- There is no satisfactory alternative treatment: documented failure (lack of efficacy or a contra-indication) to at least 3 standard therapies (corticosteroids, cytotoxic agents, immunomodulatory therapy, and Imatinib mesylate) at the appropriate duration and dose or demonstrated clinical benefit from prior treatment with mepolizumab; and
- There is reason to believe that the benefit:risk ratio for mepolizumab in the indication is positive. |
1. Según Procedimiento Local, se puede obtener el consentimiento informado escrito del sujeto o de un representante legalmente autorizado, si aplica.
2. 12 o más años de edad.
3. Cumple el criterio de diagnóstico de HES definido como:
- Eosinofilia en sangre > 1.500 eosinófilos/µl durante al menos 6 meses con evidencia de síntomas y signos con implicación o disfunción de un sistema de órganos que puede relacionarse directamente con eosinofilia (sin evidencia de parásitos, alergias u otras casusas reconocidas de eosinofilia como enfermedad del tejido conectivo, malignidad)
o
- Eosinofilia en sangre > 1.500 eosinófilos/µl durante menos de 6 meses y que cumple el otro criterio de HES acompañado de una evidencia clara de infiltración tisular eosinófila y con exclusión de la cause secundaria de eosinofilia como arriba
4. Podrán participar los pacientes que cumplan los tres criterios siguientes:
- La indicación, SHE, es una enfermedad gravemente debilitante o potencialmente mortal;
- No existe un tratamiento alternativo satisfactorio: fracaso documentado (falta de eficacia o contraindicación) de al menos 3 tratamientos convencionales con la duración y la dosis adecuadas o beneficio clínico demostrado del tratamiento previo con mepolizumab; y
- Hay motivos para creer que la relación entre los beneficios y los riesgos del mepolizumab en la indicación es favorable. |
|
E.4 | Principal exclusion criteria |
1. Subjects without HES but with other conditions associated with
Eosinophilic pathological processes such as Eosinophilic Granulomatosis with Polyangiitis [EGPA], Wegener's Granulomatosis, atopic disorders, parasitic infections, eosinophilic gastroenteropathies.
2. Female subjects of childbearing potential who are not using a highly effective method of contraception:
Consistent and correct use of an acceptable method of birth control for one month prior to the start of the investigational product and until 16 weeks after the last dose (see Section 12.2 of the protocol for a list of acceptable methods of contraception).
3. Pregnant or lactating females
4. Subjects with severe/life-threatening underlying disease unrelated to HES where life expectancy is estimated to be less than 3 months
5. Subjects with a history of or current malignancy:
- Subjects with a history of or current lymphoma
- Subjects with current malignancy or previous history of cancer in remission for less than 12 months prior to the first dose. Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded.
6. Subjects with history of serious allergic reaction (hypersensitivity/anaphylaxis) to anti-IL5 or other antibody therapy or known or suspected hypersensitivity to any component of mepolizumab, leading to treatment discontinuation.
7. Subjects with current drug or alcohol abuse where uncertain compliance with the protocol and/or with the medical management instruction of the
investigator may cause safety risk.
8. Subjects who have received treatment with an investigational agent (biologic or nonbiologic, excluding mepolizumab) within the past 30 days or 5 drug half-lives whichever is longer, prior to the administration of mepolizumab under this protocol. The term "investigational" applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products. |
1. Pacientes que no tienen HES, pero sí otras condiciones asociadas con un proceso patológico eosinofílico como granulomatosis eosinofílica con polivasculitis (GEPV), granulomatosis de Wegener, trastornos atópicos, infecciones parasitarias, gastroenteropatías eosinofílicas.
2. Mujeres con capacidad de procrear que no están usando un método anticonceptivo altamente efectivo: Uso consistente y correcto de un método anticonceptivo aceptable durante al menos un mes antes de iniciar el producto en investigación y hasta 16 semanas después de la última dosis de medicación del estudio (véase la Sección 12.2 del Protocolo para una lista de métodos anticonceptivos aceptables).
3. Mujeres embarazadas o en periodo de lactancia.
4. Pacientes con una enfermedad severa/potencialmente mortal subyacente, no relacionada con el HES, donde la esperanza de vida se estima que sea menor de 3 meses.
5. Pacientes con antecedentes o presencia de malignidad:
- Pacientes con antecedentes o presencia de linfoma
- Pacientes con neoplasia maligna en la actualidad o antecedente de cáncer en remisión durante menos de 12 meses antes de la primera dosis. No se excluirá a los pacientes con carcinoma localizado (por ejemplo, basocelular o espinocelular) de la piel que se haya extirpado para curación.
6. Pacientes con antecedentes de reacción alérgica grave (hipersensibilidad/anafilaxia) a la anti IL-5 u otra terapia con anticuerpos o conocimiento o sospecha de hipersensibilidad a cualquier componente de mepolizumab, llevando a la interrupción del tratamiento.
7. Pacientes que en la actualidad consumen drogas o alcohol, en los que el cumplimiento con el protocolo y/o con la medicación del estudio causa riesgo de seguridad.
8. Sujetos que han recibido tratamiento con un producto en investigación (biológico o no biológico, excluyendo el mepolizumab) en los últimos 30 días previos de la administración de mepolizumab de este protocolo o 5 semividas del fármaco en investigación, lo que dure más tiempo. El término "en investigación" se aplica a cualquier medicamento no aprobado para la venta en el país en el que se está utilizando o formulaciones en investigación de productos comercializados. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Serious AEs (SAEs).
Non-serious AEs related to mepolizumab as assessed by the investigator |
AA graves (AAG).
Los AAs relacionados con mepolizumab a criterio del investigador. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Each clinic visit |
En cada visita. |
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E.5.2 | Secondary end point(s) |
Mean 28-day SC dose (mg) for the last 3 administrations. |
Mean 28-day SC dose (mg) for the last 3 administrations. |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Each clinic visit |
En cada visita. |
|
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 | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Compassionate Use |
Uso compasivo. |
|
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 | Yes |
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) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
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 | 10 |
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 | Information not present in EudraCT |
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 |
|
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
|
End of trial is specified when last subject last patient has been reached. |
Última 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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |