E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Macula oedema secondary to branch retinal vein occlusion. |
Edema macular secundario a oclusión de rama venosa retiniana. |
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E.1.1.1 | Medical condition in easily understood language |
Blockage of veins in the eye that leads to build up of fluid causing swelling in the area of the retina called the macula. This may lead to damage to the macula which affects your central vision. |
Obstrucción de las venas del ojo que conduce a la acumulación de líquido que causa hinchazón en el área de la retina llamada mácula. Esto puede llevar a daño a la mácula, que afecta la visión central. |
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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 | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10025415 |
E.1.2 | Term | Macular oedema |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10038907 |
E.1.2 | Term | Retinal vein occlusion |
E.1.2 | System Organ Class | 10015919 - Eye disorders |
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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 compare the efficacy and safety of Ozurdex vs. Lucentis in subjects with BRVO. |
Comparar la eficacia y la seguridad de Ozurdex vs. Lucentis en sujetos con ORVR. |
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E.2.2 | Secondary objectives of the trial |
Not applicable. |
No aplicable. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female, ? 18 years of age 2. Written informed consent has been obtained 3. Written Data Protection Consent (European sites only) has been obtained 4. Study eye must have clear ocular media and adequate pupil dilation to permit good quality photographic imaging 5. ME secondary to BRVO in the study eye with all of the following characteristics: a) involving the centre of the macula (fovea) b) central retina subfield thickness more or equal 320 ?m as assessed with Spectralis optical coherence tomography (OCT) or more or equal 300 ?m as assessed with Cirrus OCT c) less than 90 days from onset of BRVO symptoms to screening visit d) visual acuity (VA) decrease attributable to retinal oedema Note: Characteristics a and b will be confirmed by a CRC 6. Absence of severe macular ischemia (defined as an area of nonperfusion > 4 disc areas [DA] which involve the foveal avascular zone), as confirmed by a CRC 7. BCVA score of ? 20 to ? 70 letters (20/40 to 20/400 Snellen equivalent) using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol at both the screening visit and day 1 visit. 8. Female subjects of childbearing potential must have a negative urine pregnancy test at the screening (day -14) visit. |
1.Hombre o mujer, mayor o igual a 18 años de edad 2.Obtención del consentimiento informado por escrito 3.Obtención del consentimiento de protección de datos por escrito (sólo en centros europeos) 4.El ojo de estudio debe tener los medios oculares transparentes y una dilatación pupilar adecuada para permitir la toma de imágenes fotográficas de buena calidad. 5.EM secundario a ORVR en el ojo de estudio con todas las características siguientes: a)afectación del centro de la mácula (fóvea) b)Espesor del subcampo central de la retina mayor o igual a 320 micrometros, según una evaluación realizada mediante tomografía de coherencia óptica (TCO) Spectralis, o mayor o igual a 300 micrometros, según una evaluación realizada mediante TCO Cirrus c)inicio de los síntomas de ORVR a menos de 90 días de la visita de selección d)disminución de la agudeza visual (AV) atribuible al edema retiniano Nota: Las características a y b serán confirmadas por el CLC 6.Ausencia de isquemia macular severa (definida como la existencia de un área no perfundida > 4 áreas de disco [AD] que afectan a la zona avascular de la fóvea), confirmado por el CLC 7.Puntuación MAVC mayor o igual 20 y menor o igual 70 letras (de 20/40 a 20/400 en su equivalente de Snellen) evaluada mediante el protocolo de agudeza visual del estudio de tratamiento precoz de la retinopatía diabética (ETDRS), tanto en la visita de selección como en la visita del día 1. 8.Los sujetos femeninos en edad fértil deberán tener una prueba de embarazo en orina negativa en la visita de selección (día -14). |
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E.4 | Principal exclusion criteria |
1. History of a medical condition (disease, metabolic dysfunction, physical examination finding or clinical laboratory finding) that, in the opinion of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of study medication. 2. Ocular hypertension unless controlled with monotherapy. 3. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive urine (human chorionic gonadotropin [hCG] > 20 mIU/ml) or serum pregnancy test (hCG ? 5 mIU/ml). 4. Pre-menopausal women of child-bearing potential not using adequate contraception. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant. This includes women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means unless they meet the following definition of postmenopausal:12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels of > 40 mIU/m or 6 weeks post surgical bilateral oophorectomy with or without hysterectomy. Adequate contraception is defined as one or more of the following methods: surgical sterilization (eg, bilateral tubal ligation), hormonal contraception (implantable, patch, oral), and double-barrier methods (any double combination of intrauterine device, male or female condom with spermicidal gel, diaphragm, sponge, or cervical cap). Acceptable methods of contraception may include total abstinence at the discretion of the investigator in cases where the age, career, lifestyle, or sexual orientation of the subject ensures compliance. Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the study and for 30 days after the administration of the last study drug injection. Note: Instruct females of childbearing potential to immediately inform the investigator if they become pregnant during the study. Should this occur, the investigator shall immediately contact the Sponsor as detailed in Sections 9.2 and 9.3 of the protocol. 5. Participation in an investigational drug or device study within 30 days of the screening visit 6. Any current or history of ocular disease in the study eye other than RVO that, in the opinion the investigator, may confound assessment of the macula or affect central vision, such as exudative age-related macular degeneration, geographic atrophy, diabetic retinopathy, uveitis, angioid streaks, histoplasmosis, pathological myopia, retinal detachment, epiretinal membrane, macular hole, or significant cataract 7. History of cataract surgery in either eye within the past 3 months prior to the screening visit 8. History or evidence of serious ocular trauma or intraocular surgery (such as laser-assisted in situ keratomileusis, keratoplasty, vitrectomy) in the study eye within the past 6 months prior to the screening visit 9. History of severe or serious hypersensitivity to any components of the test article or fluorescein dye. 10. > 10-Letter improvement in BCVA between the screening visit and day 1 11. Brisk afferent pupillary defect (ie, obvious and unequivocal) 12. Aphakia in the study eye or violation of the posterior capsule in the study eye, unless it occurred as a result of a yttrium-aluminum-garnet laser posterior capsulotomy in association with prior, posterior intraocular lens implantation 13. Any active ocular infection (ie, bacterial, viral, parasitic, or fungal) in adnexa of either eye 14. History of radial optic neurotomy or sheathotomy 15. Laser photocoagulation for ME in the study eye within 3 months prior to the screening visit 16. Anticipated need for ocular surgery or ophthalmic laser treatment in the study eye during the 12-month study period 17. Prior anti-VEGF treatment in study or fellow eye within 3 months of screening or systemic anti-VEGF treatment within 6 months of the screening visit 18. Use of intraocular, intravitreal, or peri-ocular steroids in the study eye within 3 months of the screening visit 19. Use of systemic steroids (eg, oral, intravenous, intra-articular, epidural, intrabursal) within 1 month of screening or anticipated use at any time during the study. Inhaled and intranasal steroids are allowed. 20. IOP > 22 mm Hg at screening or day 1 visit in either eye. |
1.Antecedentes de afecciones médicas (enfermedades, disfunciones metabólicas, hallazgos de exploraciones físicas o hallazgos de análisis clínicos) que impedirían el cumplimiento de las visitas de estudio programadas, la finalización del estudio o la administración segura del medicamento de estudio. 2.Hipertensión ocular, salvo que esté controlada con monoterapia 3.Mujeres embarazadas o en periodo de lactancia, 4.Mujeres premenopáusicas en edad fértil que no utilicen métodos anticonceptivos adecuados. 5. Participación en un estudio sobre un fármaco o dispositivo en investigación a menos de 30 días de la visita de selección 6.Cualquier antecedente de enfermedad ocular o enfermedad ocular actual del ojo de estudio, aparte de OVR, que en opinión del investigador pueda confundir la evaluación de la mácula o afectar a la visión central, como sucede en los siguientes casos: degeneración macular exudativa relacionada con la edad, atrofia geográfica, retinopatía diabética, uveítis, estrías angioides, histoplasmosis, miopía patológica, desprendimiento de retina, membrana epirretiniana, agujero macular o catarata significativa 7.Antecedentes de cirugía de catarata en cualquiera de los ojos en los últimos 3 meses anteriores a la visita de selección 8.Antecedentes o evidencia de traumatismo ocular importante o cirugía intraocular (como queratomileusis in situ asistida por láser, queratoplastia o vitrectomía) en el ojo de estudio en los últimos 6 meses antes de la visita de selección 9.Antecedentes de hipersensibilidad grave o severa en cualquiera de los componentes del artículo de prueba o tinte de fluoresceína. 10.Mejora de 10 letras en la MAVC entre la visita de selección y el día 1 11.Defecto pupilar aferente rápido (es decir, obvio e inequívoco) 12.Afaquia en el ojo de estudio o compromiso de la cápsula posterior del ojo de estudio, salvo que sea el resultado de una capsulotomía posterior mediante láser de itrio-aluminio-granate asociada a la implantación previa de una lente intraocular posterior 13.Cualquier infección ocular activa (es decir, bacteriana, vírica o fúngica) en los anexos de cualquier ojo 14.Antecedentes de neurotomía óptica radial o descompresión de la vaina del nervio óptico 15.Fotocoagulación con láser para tratar un EM en el ojo de estudio en los 3 meses anteriores a la visita de selección 16.Necesidad anticipada de cirugía ocular o tratamiento oftalmológico con láser en el ojo de estudio durante el periodo de 12 meses del estudio 17.Tratamiento previo anti-FCEV en el ojo de estudio o el ojo contralateral a menos de 3 meses de la selección o tratamiento sistémico anti-FCEV a menos de 6 meses de la visita de selección 18.Uso intraocular, intravítreo o periocular de esteroides en el ojo de estudio a menos de 3 meses de la visita de selección 19.Uso de esteroides sistémicos (por ejemplo, orales, intravenosos, intraarticulares, epidurales o intrabursales) a menos de 1 mes de la selección o uso anticipado de los mismos en cualquier momento del estudio. Se permite el uso de esteroides inhalados e intranasales. 20.PIO > 22 mm de Hg en la visita de selección o del día 1 en cualquier de los ojos. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy variable is mean change in BCVA at month 12. |
La variable principal de eficacia es la variación media de la MAVC (mejor agudeza visual corregida) en el mes 12. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
BCVA assessment at screening, baseline, day 7 and at each monthly visit. |
Evaluación BCVA en la visita de selección, de referencia, dia 7 y en cada visita mensual. |
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E.5.2 | Secondary end point(s) |
1. Mean change in the central retina subfield thickness between baseline and month 6, and between baseline and month 12 2. Proportion of subjects with ? 15-letter improvement in BCVA between baseline and month 12 3. Proportion of subjects with ? 15-letter decrease in BCVA between baseline and month 12 4. Change from baseline in vision-dependent subfields of the VFQ-25 questionnaire including near vision, far vision, and vision-dependent activity at month 3, month 6, and month 12. |
1.Variación media del espesor del subcampo central de la retina entre el inicio y el mes 6, y entre el inicio y el mes 12. 2.Proporción de sujetos con mejoras ? 15 letras en la MAVC entre el inicio y el mes 12. 3.Proporción de sujetos con disminuciones ? 15 letras en la MAVC entre el inicio y el mes 12. 4.Variación de las mediciones en los subcampos dependientes de la visión en el cuestionario VFQ-25, incluidas la visión de cerca, la visión de lejos y la actividad desde la visita basal a los 3, 6 y 12 meses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. OCT assessments that will be used in evaluation of timepoint will be done at baseline, month 6 and month 12. 2. and 3. BCVA assessments that will be used in evaluation of timepoints will be done at baseline and month 12. 4. VFQ-25 questionnaire completed at baseline, month 3, month 6, and month 12. |
1. Evaluaciones de OTC que serán usadas en la evaluación de la variable principal serán hechas en la visita de referencia, mes 3, mes 6 y mes 12. 2. y 3. Evaluaciones de BCVA que seránm usadas en la evaluación de los tiempos de evaluación serán hechas en la visita de referencia y mes 12. 4. Cuestionario VFQ-25 se completará en visita de referencia, mes 3, mes 6 y mes 12. |
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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 | 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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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) | 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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 34 |
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 |
France |
Germany |
Israel |
Italy |
Spain |
United Kingdom |
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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
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Last visit last subject |
Última visita del último sujeto |
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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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |