E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Generalized Myasthenia Gravis |
Miastenia gravis generalizada |
|
E.1.1.1 | Medical condition in easily understood language |
Generalized Myasthenia Gravis |
Miastenia gravis generalizada |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10071942 |
E.1.2 | Term | Myasthenia gravis and related conditions |
E.1.2 | System Organ Class | 100000004859 |
|
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 ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile. |
Evaluar la eficacia de ravulizumab en comparación con el placebo en el tratamiento de la MGg basándose en la mejora del perfil de miastenia gravis-actividades de la vida diaria (MG-AVD). |
|
E.2.2 | Secondary objectives of the trial |
To assess the efficacy of ravulizumab compared with placebo in the treatment of gMG based on the improvement in the Quantitative Myasthenia Gravis (QMG) total score. |
Evaluar la eficacia de ravulizumab en comparación con el placebo en el tratamiento de la MgG basándose en la mejora de la puntuación total de miastenia gravis cuantitativa (MGC). |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Male and female patients ≥ 18 years of age • Diagnosed with MG at least 6 months (180 days) prior to the date of the Screening Visit as confirmed by protocol-specific criteria • Myasthenia Gravis Foundation of America Clinical Classification Class II to IV at screening • MG-ADL profile must be ≥ 6 at screening and randomization (Day 1) • Vaccinated against meningococcal infections within 3 years prior to, or at the time of, initiating study drug to reduce the risk of meningococcal infection (N meningitidis). • Body weight ≥ 40 kg at the time of screening • Patients of childbearing potential and patients with partners of childbearing potential must follow protocol-specified contraception guidance for avoiding pregnancy while on treatment and for 8 months after last dose of study drug |
• Hombres y mujeres deben tener ≥18 años de edad • Diagnóstico de miastenia gravis (MG) al menos 6 meses (180 días) antes de la fecha de la visita de selección, según lo confirmen los criterios específicos del protocolo (ver a continuación). • Clase II a IV en la selección según la clasificación clínica de la Myasthenia Gravis Foundation of America (Fundación de América para la Miastenia Grave). • El perfil de MG-ADL debe ser ≥ 6 en la selección y la aleatorización (día 1). • Para reducir el riesgo de infección meningocócica (N meningitidis), todos los pacientes se deben haber vacunado contra infecciones meningocócicas en los 3 años previos al inicio del medicamento del estudio o en dicho momento. Los pacientes que inicien tratamiento con el medicamento del estudio menos de 2 semanas después de recibir una vacuna antimeningocócica deben recibir tratamiento con antibióticos profilácticos adecuados hasta 2 semanas después de la vacunación. • Las pacientes con capacidad para tener hijos y los pacientes con parejas con capacidad para tener hijos deben seguir la guía sobre anticoncepción especificada en el protocolo para evitar el embarazo mientras reciban el tratamiento y durante 8 meses después de la última dosis del medicamento del estudio. |
|
E.4 | Principal exclusion criteria |
Medical Conditions: • Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥ 5 years before Screening • History of thymectomy within the 12 months prior to screening • History of N meningitidis infection • Human immunodeficiency virus (HIV) infection • History of hospitalization for ≥ 24 hours, for any reason, within the 4 weeks (28 days) prior to screening • Females who plan to become pregnant during the study, or are currently pregnant or breastfeeding, or who have a positive pregnancy test result at screening or on Day 1
Prior/Concomitant Therapy •Use of the following within the time period specified below: - IVIg within the 4 weeks (28 days) prior to randomization (Day 1) - Use of PE within the 4 weeks (28 days) prior to randomization (Day 1) - Use of rituximab within the 6 months (180 days) prior to screening • Patients who have received previous treatment with complement-inhibitors (eg, eculizumab) |
Afecciones médicas • Cualquier timoma activo o sin tratar. Antecedentes de carcinoma tímico o neoplasia tímica a menos que se considere curada por un tratamiento adecuado sin evidencia de recidiva durante ≥ 5 años antes de la selección. • Antecedentes de timectomía en los 12 meses anteriores a la selección. • Antecedentes de infección por N meningitidis. • Infección por el virus de inmunodeficiencia humana (VIH) (que se pone de manifiesto mediante valoración de anticuerpos contra el VIH-1 o VIH-2). • Antecedentes de hospitalización durante ≥ 24 horas, por cualquier motivo en las 4 semanas (28 días) anteriores a la selección. • Pacientes de sexo femenino que planean quedarse embarazadas o que están actualmente embarazadas o en período de lactancia. • Pacientes de sexo femenino que han obtenido un resultado positivo en una prueba de embarazo en la selección o el día 1.
• Pacientes que hayan recibido tratamiento previo con inhibidores del sistema del complemento (p. ej., eculizumab). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from Baseline in MG-ADL total score |
Cambio respecto al inicio en la puntuación total de MG-AVD en la semana 26 del período aleatorizado-controlado. |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
At Week 26 of the Randomized-Controlled Period. |
Variación respecto al inicio de la puntuación de MGC en la semana 26 |
|
E.5.2 | Secondary end point(s) |
Change from Baseline in QMG total score |
Variación respecto al inicio de la puntuación de MGC |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
At Week 26 |
En la semana 26 |
|
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 | Yes |
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 | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
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 | Yes |
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 | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 32 |
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 |
Austria |
Canada |
Denmark |
Germany |
Israel |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Spain |
Switzerland |
United States |
|
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 in the study or last scheduled procedure shown in the Schedule of Activities for the last patient in the study globally |
Última visita del último paciente o el último procedimiento programado indicado en el Programa de actividades. |
|
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 | 6 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |