E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Central retinal vein occlusion |
Oclusión de la vena central de la retina |
|
E.1.1.1 | Medical condition in easily understood language |
Central retinal vein occlusion |
Oclusión de la vena central de la retina |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Eye Diseases [C11] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10007972 |
E.1.2 | Term | Central retinal vein occlusion |
E.1.2 | System Organ Class | 100000004853 |
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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 demonstrate that brolucizumab is non-inferior to aflibercept with respect to the change in visual acuity from baseline up to month 6 |
Demostrar que brolucizumab no es inferior a aflibercept con respecto al cambio de agudeza visual mejor corregida (AVMC) desde la basal al mes 6. |
|
E.2.2 | Secondary objectives of the trial |
1. To assess the effect of brolucizumab as compared to aflibercept on visual acuity 2. To evaluate the anatomical outcome with brolucizumab relative to aflibercept 3. To evaluate the treatment frequency with brolucizumab during the individualized flexible treatment (IFT) period relative to aflibercept 4. To assess the safety and tolerability of brolucizumab relative to aflibercept 5. To evaluate the effect of brolucizumab relative to aflibercept on patient-reported vision-related quality of life (VFQ-25) 6. To assess the immunogenicity of brolucizumab |
. Evaluar el efecto de brolucizumab respecto a aflibercept en la AVMC. 2. Evaluar el resultado anatómico con brolucizumab respecto a aflibercept. 3. Evaluar la frecuencia del tratamiento con brolucizumab durante el periodo de tratamiento flexible individualizado (TFI) respecto a aflibercept. 4. Evaluar la seguridad y tolerabilidad de brolucizumab respecto a aflibercept. 5. Evaluar el efecto de brolucizumab respecto a aflibercept en la calidad de vida relacionada con la visión comunicada por el paciente. 6. Evaluar la inmunogenicidad de brolucizumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1- Signed informed consent must be obtained prior to participation in the study 2- Male or female patients to be 18 years of age or over at screening 3- Patients with visual impairment due to ME secondary to CRVO diagnosed less than 6 months prior to screening; hemiretinal vein occlusion will be classified as CRVO (study eye) 4- BCVA score between 78 and 23 letters, inclusive, using ETDRS visual acuity testing charts (approximate Snellen equivalent of 20/32 to 20/320) at both screening and baseline (study eye) |
-Se deberá obtener el consentimiento informado firmado antes de la participación en el estudio. -Pacientes de ambos sexos >/=18 años de edad en la selección. -Pacientes con alteración visual debida a EM secundario a OVCR diagnosticado <6 meses antes de la selección; la oclusión venosa hemirretiniana se clasificará como OVCR (ojo en estudio). -Puntuación de la agudeza visual mejor corregida (AVMC) entre 78 y 23 letras, ambas inclusive, utilizando optotipos de agudeza visual del Estudio del tratamiento precoz de la retinopatía diabética (ETDRS) (equivalente de Snellen aproximado de 20/32 a 20/320) tanto en la visita de selección como en la basal (ojo en estudio). |
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E.4 | Principal exclusion criteria |
1-Concomitant conditions or ocular disorders in the study eye at screening or baseline which could, in the opinion of the investigator, prevent response to study treatment or may confound interpretation of study results, compromise visual acuity or require medical or surgical intervention during the first 12-month study period (e.g. structural damage of the fovea, vitreous hemorrhage, retinal vascular occlusion other than BRVO, retinal detachment, macular hole, or choroidal neovascularization of any cause, diabetic retinopathy (except mild non-proliferative) and diabetic macular edema). Hemiretinal vein occlusion should be excluded. 2-Any active intraocular or periocular infection or active intraocular inflammation (e.g. infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis, uveitis) in study eye at screening or baseline 3-Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication, or according to investigator’s judgment, at screening or baseline 4-Presence of amblyopia, amaurosis or ocular disorders in the fellow eye with BCVA < 20/200 at screening (except when due to conditions whose surgery may improve VA, e.g. cataract) 5-Previous treatment with any anti-VEGF therapy or investigational drugs in the study eye at any time prior to baseline 6-Previous use of intraocular or periocular steroids in study eye at any time prior to baseline 7-Macular laser photocoagulation (focal/grid) in the study eye at any time prior to baseline and peripheral laser photocoagulation in the study eye within 3 months prior to the baseline 8-Intraocular surgery in the study eye during the 3-month period prior to baseline 9-Vitreoretinal surgery in the study eye at any time prior to baseline 10-Aphakia with the absence of posterior capsule in the study eye |
1. Problemas concomitantes o trastornos oculares en el ojo en estudio en la selección o la basal que podrían, a criterio del investigador, impedir la respuesta al tratamiento del estudio o confundir la interpretación de los resultados del estudio, comprometer la agudeza visual o precisar intervención médica o quirúrgica durante el primer periodo de 12 meses del estudio (p. ej., daños estructurales de la fóvea, hemorragia del vítreo, oclusión vascular retiniana, salvo ORVR, desprendimiento de la retina, hueco macular o neovascularización coroidea por cualquier causa, retinopatía diabética [excepto la no proliferativa leve] y edema macular diabético). 2. Cualquier infección intraocular o periocular activa o inflamación intraocular activa (p. ej., conjuntivitis infecciosa, queratitis, escleritis, endoftalmitis, blefaritis infecciosa, uveítis) en el ojo en estudio en la selección o la basal. 3. Glaucoma no controlado en el ojo en estudio definido como presión intraocular (PIO) >25 mmHg con la medicación o a juicio del investigador, en la selección o la basal. 4. Presencia de ambliopía, amaurosis o trastornos oculares en el ojo contralateral con AVMC <20/200 en la selección (excepto en caso de enfermedades cuya cirugía pueda mejorar la AV, p. ej., cataratas). 5. Tratamiento previo con cualquier tratamiento anti-VEGF o fármaco en investigación en el ojo en estudio en cualquier momento anterior a la basal. 6. Uso previo de esteroides intraoculares o perioculares en el ojo en estudio en cualquier momento anterior a la basal. 7. Fotocoagulación macular con láser (focal/en rejilla) en el ojo en estudio en cualquier momento anterior a la basal y fotocoagulación periférica con láser en el ojo en estudio durante los 3 meses anteriores a la basal. 8. Cirugía intraocular en el ojo en estudio durante el periodo de 3 meses antes de la basal. 9. Cirugía vitreorretiniana en el ojo en estudio en cualquier momento anterior a la basal. 10. Afaquia con ausencia de cápsula posterior en el ojo en estudio -Tratamientos oculares: tratamiento previo con cualquier fármaco o fármaco en investigación del factor de crecimiento endotelial antivascular (VEGF), esteroides intraoculares o perioculares, fotocoagulación macular con láser (focal/en rejilla), cirugía vitreorretiniana (ojo en estudio). |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in BCVA at Week 24 |
Cambio de agudeza visual mejor corregida (AVMC) desde visita basal a la semana 24 |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Baseline and Week 24 |
Visita Basal y semana 24 |
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E.5.2 | Secondary end point(s) |
1. • Change from baseline in BCVA averaged over Week 40 to Week 52 and Week 64 to Week 76 • Change from baseline in BCVA by visit up to Week 76 • Proportion of study eyes with a gain ≥ 5, 10 and 15 letters in BCVA by visit compared to baseline • Proportion of study eyes with a loss ≥ 5, 10 and 15 letters in BCVA by visit compared to baseline 2. • Change from baseline in central subfield thickness (CSFT, derived from SD-OCT) averaged over Week 40 to Week 52 and Week 64 to Week 76 • Change from baseline in CSFT (derived from SD-OCT) by visit up to Week 76 • Proportion of study eyes with presence of retinal fluid (intra- and/or subretinal fluid) by visit up to Week 76 (derived from SD-OCT) • Proportion of study eyes with a CSFT < 300 μM (derived from SD-OCT) by visit up to Week 76 3. • Number of injections between Week 24 and Week 52 and between Week 24 and Week 76 • Time to first re-treatment between Week 24 and Week 76 4. • Incidence of ocular and non-ocular Adverse Events up to Week 52 and Week 76 5. • Change from baseline in patient reported outcomes (NEI VFQ-25) at Week 24, Week 52 and Week 76 6. • Anti-drug antibody status at baseline and Week 4, Week 12, Week 24, Week 36, Week 52 and Week 76 |
1 -Cambio medio respecto a la basal en la AVMC durante el periodo de la semana 40 a la semana 52 y de la semana 64 a la semana 76. -Cambio respecto a la basal en la AVMC por visita hasta la semana 76. -Proporción de ojos en estudio con una ganancia >/=5, 10 y 15 letras en la AVMC por visita respecto a la basal. -Proporción de ojos en estudio con una pérdida >/=5, 10 y 15 letras en la AVMC por visita respecto a la basal. 2 -Cambio medio respecto a la basal en el grosor del subcampo central (GSC) durante el periodo de la semana 40 a la semana 52 y de la semana 64 a la semana 76. -Cambio respecto a la basal en el GSC por visita hasta la semana 76. -Proporción de ojos en estudio con presencia de líquido retiniano (intrarretiniano o subretiniano) por visita hasta la semana 76 (derivado de la SD-OCT). -Proporción de ojos en estudio con un GSC <300 μM por visita hasta la semana 76. 3 -Número de inyecciones entre la semana 24 y la semana 52 y entre la semana 24 y la semana 76. -Tiempo hasta el primer reinicio del tratamiento entre la semana 24 y la semana 76. 4 -Incidencia de AA oculares y no oculares hasta la semana 52 y la semana 76. 5 -Cambio respecto a la basal en los resultados comunicados por el paciente (NEI VFQ-25) en las semanas 24, 52 y 76. 6 -Estado de anticuerpos contra el fármaco en la basal y en las semanas 4, 12, 24, 36, 52 y 76. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline, Weeks 4, 12, 24, 36, 40, 52, 64 and/or 76 |
Visita Basal, semanas 4, 12, 24, 36, 40, 52, 64 y/o 76 |
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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 | Yes |
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 | Yes |
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) | Yes |
E.8.2.2 | Placebo | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 44 |
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 |
Canada |
China |
Czech Republic |
Finland |
France |
Germany |
Greece |
Hungary |
Italy |
Japan |
Malaysia |
Netherlands |
Russian Federation |
Spain |
Thailand |
Turkey |
United Kingdom |
United States |
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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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
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 |