E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Paroxysmal Nocturnal Hemoglobinuria |
Hemoglobinuria paroxística nocturna |
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E.1.1.1 | Medical condition in easily understood language |
Paroxysmal Nocturnal Hemoglobinuria |
Hemoglobinuria paroxística nocturna |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10055629 |
E.1.2 | Term | Paroxysmal nocturnal hemoglobinuria |
E.1.2 | System Organ Class | 100000004857 |
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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 PK noninferiority of ravulizumab SC versus ravulizumab IV in adult patients with PNH |
Evaluar la FC de no inferioridad de ravulizumab s.c. frente a ravulizumab i.v. en pacientes con HPN |
|
E.2.2 | Secondary objectives of the trial |
- To characterize PK of ravulizumab SC - To characterize PD of ravulizumab SC - To characterize immunogenicity of ravulizumab SC - To evaluate HRQoL and treatment satisfaction on ravulizumab SC - To evaluate safety of ravulizumab SC and ravulizumab OBDS - To evaluate efficacy of ravulizumab SC - To assess performance of ravulizumab OBDS |
- Caracterizar la FC de ravulizumab s.c. - Caracterizar la FD de ravulizumab s.c. - Caracterizar la inmunogenia de ravulizumab s.c. - Evaluar la CdVRS y la satisfacción con el tratamiento con ravulizumab s.c. - Evaluar la seguridad de ravulizumab s.c. y el SAC de ravulizumab - Evaluación de la eficacia de ravulizumab s.c. - Evaluación del rendimiento del SAC de ravulizumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Age 1. Patients must be at least 18 years of age at the time of signing the informed consent.
Patient and Disease Characteristics 2. Treated with eculizumab according to the labeled dosing recommendation for PNH (900 mg every 14 days ± 2 days) for at least 6 months prior to study entry with no missed doses within 2 months prior to study entry and no more than 2 doses outside of the visit window. 3. Lactate dehydrogenase levels ≤ 1.5 × ULN (upper limit of normal), according to central laboratory, at Screening. Sample must be obtained within 24 hours of or immediately prior to a scheduled eculizumab dose administration (ie, at trough eculizumab level). 4. Documented diagnosis of PNH confirmed by high-sensitivity flow cytometry evaluation (Borowitz, Craig et al. 2010). 5. 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). |
Edad 1.Los pacientes deben tener, al menos, 18 años en el momento de firmar el consentimiento informado.
Características del paciente y de la enfermedad 2.Tratado con eculizumab de acuerdo con la recomendación posológica de la ficha técnica para la HPN (900 mg cada 14 días ± 2 días) durante, al menos, 6 meses antes de la incorporación al estudio y que no se haya saltado ninguna dosis en los 2 meses previos a la incorporación al estudio y no más de 2 dosis fuera del margen de la visita. 3.Niveles de lactato deshidrogenasa ≤ 1,5 × LSN (límite superior de la normalidad), de acuerdo con el laboratorio central, en la selección. La muestra se debe obtener en las 24 horas previas o inmediatamente antes de una administración de dosis de eculizumab programada (es decir, con el nivel mínimo de eculizumab). 4.Diagnóstico documentado de HPN confirmado mediante evaluación con citometría de flujo de alta sensibilidad (Borowitz, 2010). 5.Vacunado contra infecciones meningocócicas en los 3 años previos al inicio del fármaco del estudio o en dicho momento, para reducir el riesgo de infección meningocócica (N. meningitidis). |
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E.4 | Principal exclusion criteria |
Medical Conditions 1. More than 1 LDH value > 2 × ULN within the 6 months prior to study entry. 2. Major adverse vascular event (MAVE) in the 6 months prior to study entry. 3. Platelet count < 30,000/mm3 (30 × 109/L) at Screening. 4. Absolute neutrophil count < 500/μL (0.5 × 109/L) at Screening. 5. History of bone marrow transplantation. 6. History of N meningitidis infection. |
Afecciones médicas 1.Más de 1 valor de LDH > 2 × LSN a lo largo de los 6 meses previos a la incorporación al estudio. 2.Acontecimiento adverso vascular importante (AAVI) en los 6 meses previos a la incorporación al estudio. 3.Recuento plaquetario ≤ 30 000/mm3 (30 × 109/l) en la selección. 4.Recuento absoluto de neutrófilos < 500/µl (0,5 × 109/l) en la selección. 5.Antecedentes de trasplante de médula ósea. 6.Antecedentes de infección por N. meningitidis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Day 71 serum ravulizumab Ctrough |
Cmín. sérica de ravulizumab del día 71 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
PK Endpoint: Ctrough over time
PD Endpoint: Free serum C5 concentrations over time
Immunogenicity
HRQoL and Treatment Satisfaction Endpoints
Safety Endpoints
Efficacy Endpoints |
Criterio de valoración FC: Cmín. a lo largo del tiempo
Criterio de valoración FD: Concentraciones séricas de C5 libre a lo largo del tiempo
Criterio de valoración de inmunogenia
Criterios de valoración de satisfacción con el tratamiento y CdVRS
Criterios de valoración de la seguridad
Criterios de valoración de la eficacia |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
throughout the study |
A lo largo 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 | 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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Pacientes en el grupo de ravulizumab IV cambiarán a 490 mg de ravulizumab SC en el período de extens |
Patients in the ravulizumab IV group will switch to 490 mg of ravulizumab SC in the extension period |
|
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 |
Ravulizumab IV |
Ravulizumab iv |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 46 |
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 |
Austria |
Belgium |
Brazil |
Canada |
Czech Republic |
Finland |
France |
Germany |
Italy |
Korea, Republic of |
Netherlands |
Russian Federation |
Spain |
Sweden |
Turkey |
United Kingdom |
United States |
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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
|
The end of the study is defined as the date of the last patient visit or safety follow up, whichever occurs later. |
El final del estudio se define como la fecha de la última visita del paciente o del último seguimiento de seguridad, lo que ocurra más tarde. |
|
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 | 11 |
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 |