E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic Macular Edema (DME) |
EDEMA MACULAR DIABÉTICO (EME) |
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E.1.1.1 | Medical condition in easily understood language |
Diabetic macular edema (DME) |
EDEMA MACULAR DIABÉTICO (EME) |
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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 | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10057934 |
E.1.2 | Term | Diabetic macular edema |
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 evaluate the efficacy of intravitreal (IVT) injections of RO6867461 on best-corrected visual acuity (BCVA) outcomes |
-Evaluar la eficacia de las inyecciones IVT de RO6867461 en relación con las variables de valoración de la MAVC |
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E.2.2 | Secondary objectives of the trial |
•To evaluate the efficacy of RO6867461 on diabetic retinopathy (DR) severity outcomes •To evaluate the efficacy of RO6867461 on additional BCVA outcomes •To evaluate the efficacy of RO6867461 on additional DR outcomes •To evaluate RO6867461 treatment intervals as specified in the protocol •To evaluate the efficacy of RO6867461 on anatomical outcome measures using spectral-domain optical coherence tomography (SD OCT) •To evaluate the efficacy of RO6867461 on patient-reported vision-related functioning and quality of life using the National Eye Institute 25-Item Visual Function Questionnaire (NEI VFQ-25) •To evaluate the ocular and systemic safety and tolerability of RO6867461 •To characterize the systemic pharmacokinetics of RO6867461 •To evaluate the immune response to RO6867461 •To evaluate potential effects of anti-drug antibodies (ADAs) |
.Evaluar la eficacia de RO6867461 en los resultados de severidad de la retinopatía diabética (DR) • Evaluar la eficacia de RO6867461 en los resultados adicionales de BCVA • Evaluar la eficacia de RO6867461 en resultados DR adicionales • Evaluar los intervalos de tratamiento RO6867461 según aparece en el protocolo • Evaluar la eficacia de RO6867461 en las medidas de resultado anatómicas utilizando la tomografía de coherencia óptica de dominio espectral (OCT) • Evaluar la eficacia de RO6867461 en el funcionamiento relacionado con la visión y la calidad de vida informada por el paciente utilizando el cuestionario de función visual de 25 ítems del National Eye Institute (NEI VFQ-25) • Evaluar la seguridad y tolerabilidad ocular y sistémica de RO6867461 • Caracterizar la farmacocinética sistémica de RO6867461 • Para evaluar la respuesta inmune a RO6867461 • Para evaluar los efectos potenciales de los anticuerpos antidrogas (ADA) |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Age >= 18 years - Documented diagnosis of diabetes mellitus (Type 1 or Type 2) - Ability and willingness to undertake all scheduled visits and assessments - For women of childbearing potential: agreement to remain abstinent or use acceptable contraceptive methods during the treatment period and for at least 3 months after the final dose of study treatment - Macular thickening secondary to DME involving the center of the fovea - Documented BCVA of 20/40 to 20/320 (letter score of 73 to 25) in the study eye at the initiation of treatment |
-Tener 18 años de edad -Diagnóstico documentado de diabetes mellitus (tipo 1 o 2) -Tener capacidad y disposición para realizar todas las visitas y evaluaciones planificadas -Las mujeres potencialmente fértiles deben comprometerse a practicar la abstinencia sexual o a usar métodos anticonceptivos aceptables durante el período de tratamiento y como mínimo, hasta 3 meses después de la administración de la última dosis del tratamiento del estudio -Engrosamiento macular secundario a EMD que afecta al centro de la fóvea -MAVCdocumentado de 20/40 a 20/320 (puntaje de letra de 73 a 25) en el ojo de estudio al inicio del tratamiento |
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E.4 | Principal exclusion criteria |
- Currently untreated diabetes mellitus or previously untreated patients who initiated oral anti-diabetic medication or insulin within 3 months prior to Day 1 - Uncontrolled blood pressure - Pregnancy or breastfeeding, or intention to become pregnant during the study
Ocular Exclusion Criteria for Study Eye - Treatment with panretinal photocoagulation within 3 months prior to Day 1 to the study eye - Macular laser within 3 months prior to Day 1 to the study eye - Any IVT or periocular corticosteroid treatment within 6 months prior to Day 1 to the study eye - Any use of medicated intraocular implants, including Ozurdex®, within 6 months of Day 1 and Iluvien® implants at any time prior to Day 1 to the study eye - Prior administration of IVT RO6867461 in either eye - Active intraocular or periocular infection or active intraocular inflammation in the study eye - Any current or history of ocular disease other than DME that may confound assessment of the macula or affect central vision in the study eye - Any current ocular condition which, in the opinion of the investigator, is currently causing or could be expected to contribute to irreversible vision loss due to a cause other than DME in the study eye |
-Pacientes con diabetes mellitus no tratada en la actualidad o no tratada previamente que han iniciado un tratamiento con antidiabéticos orales o insulina en los 3 meses previos al día 1 -Presión arterial incontrolada -Embarazo o lactancia, o intención de quedar embarazada durante el estudio Criterios de exclusión oculares para el ojo en estudio estudio -Tratamiento con fotocoagulación panretiniana (FPR) en los 3 meses previos al día 1 -Tratamiento con láser en la mácula en los 3 meses previos al día 1 -Administración de cualquier tratamiento con corticosteroides IVT o perioculares (Sub-Tenon) en los 6 meses previos al día 1 -Uso de cualquier implante intraocular inyectable, incluyendo Ozurdex®, en los 6 meses previos al día 1 Uso de implantes Iluvien® en cualquier momento antes del día 1 -Administración previa de RO6867461 IVT en cualquiera de los dos ojos - -Infección intraocular o periocular activa o inflamación intraocular activa en el ojo del estudio -Cualquier enfermedad ocular distinta de EMD, en la actualidad o en el pasado, que pueda confundir la evaluación de la mácula o afectar a la visión central del ojo en estudio -Presencia de cualquier patología macular en la actualidad que, en opinión del investigador, esté causando actualmente o pueda contribuir previsiblemente a una pérdida de visión irreversible por causas distintas a EMD en el ojo en estudio |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change from baseline in BCVA at 1 year |
Cambio desde basal en BCVA a 1 año |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. Baseline (Day 1) and 1 year |
1.Estado basal(día 1) y 1 año |
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E.5.2 | Secondary end point(s) |
1. Proportion of patients with a >= 2-step DRS improvement from baseline on the ETDRS Diabetic Retinopathy Severity Scale (DRSS) at 1 year 2. Change from baseline in BCVA over time 3. Proportion of patients gaining >=15, >=10, >= 5, or >= 0 letters in BCVA from baseline over time 4. Proportion of patients avoiding a loss of >= 15, >= 10, >= 5, or > 0 letters in BCVA from baseline over time 5. Proportion of patients with a >= 2-step DRS improvement from baseline on the ETDRS DRSS over time 6. Proportion of patients with a >= 3-step DRS improvement from baseline on the ETDRS DRSS over time 7. Proportion of patients gaining >=15 letters or achieving BCVA of >= 84 letters over time 8. Proportion of patients with BCVA Snellen equivalent of 20/40 or better over time 9. Proportion of patients with BCVA Snellen equivalent of 20/200 or worse over time 10. Proportion of patients who develop new PDR over time 11. Change from baseline in CST over time 12. Change from baseline in NEI VFQ-25 composite score over time 13. Proportion of patients with absence of DME over time 14. Incidence and severity of ocular adverse events 15. Incidence and severity of non-ocular adverse events 16. Plasma concentration of RO6867461 over time 17. Presence of ADAs during the study relative to the presence of ADAs at baseline 18. Relationship between ADA status and efficacy, safety, or PK endpoints |
DRS> = 2 inicio en la escala de gravedad de la RD (DRSS) Cambio ds la línea base en BCVA > 3.> = 15,> = 10,> = 5 o> 0 en la MAVC mejora DRS> = 2 p ds en el ETDRS DRSS DRS> = 3 pasos desde el in en el ETDRS DRSS > = 15 letras logran una MAVC de> = 84 l BCVA Snellen equivalente a 20/40 o mejor con el Snellen a 20/200 PDR l CST puntaje |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. At 1 year 2-6. Baseline to 2 years 7-10. Up to 2 years 11-12. Baseline to 2 years 13-15. Up to 2 year 16-18. Day 1, Week 4; Week 28; Week 52; Week 76; Week 100, at early termination visit |
1. Al año 2-6. Basal hasta 2 años 7-10. Hasta 2 años 11-12. Basal a 2 años 13-15. Hasta 2 años 16-18. Día 1, semana 4; Semana 28; Semana 52; Semana 76; Semana 100, en la visita de finalización anticipada |
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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 | 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 | Yes |
E.6.13.1 | Other scope of the trial description |
Immunogenicity Biomarker |
Inmunogenicidad Biomarcador |
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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 | 3 |
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 | 16 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 98 |
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 |
Argentina |
Australia |
Brazil |
Canada |
China |
Czech Republic |
Denmark |
France |
Germany |
Hong Kong |
Hungary |
Italy |
Korea, Republic of |
Netherlands |
Poland |
Portugal |
Russian Federation |
Singapore |
Spain |
Switzerland |
Taiwan |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | |
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 | 10 |