E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
diabetic retinopathy |
Retinopatía diabética |
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E.1.1.1 | Medical condition in easily understood language |
diabetic eye disease |
enfermedad ocular diabética |
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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 | 10054109 |
E.1.2 | Term | Non-proliferative diabetic retinopathy |
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 |
The main objective is to evaluate ocular and systemic safety and tolerability of BI 1467335 as well as whether BI 1467335 monotherapy has a potential to improve retinal lesions in patients with moderately severe NPDR (DRSS level 47) or severe NPDR (DRSS level 53), without CI-DME. |
El objetivo principal es evaluar la seguridad y tolerabilidad ocular y sistémica de BI 1467335 como también si BI 1467335 en monoterapia tiene el potencial de mejorar lesiones retinales en pacientes con RDNP moderadamente severa (DRSS nivel 47) o RDNP severa (DRSS nivel 53), sin EMD-PC. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Of full age (according to local legislation, usually ≥ 18 years) and ≤ 80 years at screening 2. Male or female patients. Women of childbearing potential (WOCBP)1 must be ready and able to use two methods of contraception with at least one of them being a highly effective method of birth control per ICH M3 (R2) that result in a low failure rate of less than 1% per year when used consistently and correctly. A list of contraception methods meeting these criteria is provided in the patient information. 3. Diagnosis of diabetes mellitus (type 1 or type 2): - Documented diabetes by American Diabetes Association (ADA) and/or World Health Organization criteria - Antidiabetic medication stable for ≥3 months prior to screening and expected to be stable throughout the trial (no change in medication or the dose, except for insulin the prescribed total daily dose change not more than 10%) 4. Glycosylated hemoglobin (HbA1c) ≤ 10% at screening 5. Non-proliferative diabetic retinopathy (NPDR) without center-involved diabetic macular edema (CI-DME) in the study eye at screening with NPDR level 47 or level 53, as determined by the CRC by using the DR severity scale (DRSS) 6. Best corrected visual acuity ETDRS letter score ≥ 70 letters in the study eye at screening 7. Media clarity, pupillary dilation and individual cooperation sufficient for adequate retinal examination including fundus photographs and OCT 8. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial |
1. Mayores de edad (de acuerdo con la legislación local, normalmente ≥ 18 años) y ≤ 80 años en el screening. 2. Pacientes hombres o mujeres. Las mujeres con potencial para quedarse embarazadas (WOCBP) deben estar listas y poder usar 2 métodos anticonceptivos, siendo al menos uno de ellos un método de control de la natalidad altamente efectivo según ICH M3 (R2) que resulte en un índice de error de menos de 1% por año cuando se usa de forma consistente y correcta. Una lista de métodos anticonceptivos que cumplan estos criterios se encuentra en la información al paciente. 3. Diagnóstico de diabetes mellitus (tipo 1 o tipo 2): - Diabetes documentada según criterios de la American Diabetes Association (ADA) y/o la Organización Mundial de la Salud - Medication antidiabética estable durante ≥3 antes del screening y que se espere que se mantenga estable durante el ensayo (sin cambios en la medicación o la dosis , exceptoen la insulina que la dosis total diaria prescrita no cambie más del 10%) 4.Hemoglobina glicosilada (HbA1c) ≤ 10% en el screening 5. Retinopatía diabética no proliferativa (RDNP) sin edema macular diabético de predominio central (EMD-PC) en el ojo del ensayo en el momento del screening con RDNP nivel 47 o nivel 53, determinado por el CRC usando la escala de severidad DR (DRSS) 6. Optotipos ETDRS para la mejor agudeza vsiual corregida ≥ 70 letras en el ojo del estudio en el screening 7. Claridad del medio, dilatación de la pupila y cooperación individual suficientes para un examen retinal adecuado incluyendo forografías del fundus y OCT 8. Consentimiento informado por escrito, firmado y fechado según ICH-GCP y legislación local antes de la admisión al ensayo. |
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E.4 | Principal exclusion criteria |
1. Additional eye disease in the study eye that, in the opinion of the investigator, could compromise or alter visual acuity during the course of the study (e.g. vein occlusion, uncontrolled intraocular pressure (IOP) >24 mmHg on optimal medical treatment, glaucoma with visual field loss, uveitis or other ocular inflammatory disease, vitreomacular traction, monocular vision, history of ischemic optic neuropathy, or genetic disorders such as retinitis pigmentosa) 2. Active center-involved DME (CI-DME) on clinical examination and OCT central subfield thickness above 300 μm in the study eye, as measured by Optovue OCT 3. Anterior segment and vitreous abnormalities in the study eye that would compromise the adequate assessment of the best corrected visual acuity or an adequate examination of the posterior pole 4. Evidence of neovascularization on clinical examination including active neovascularization of the iris (small iris tufts are not an exclusion) or angle neovascularization in the study eye, ruled out by gonioscopy (documented in the last 4 weeks before screening or performed at screening) 5. Prior pan-retinal photocoagulation (defined as ≥ 100 burns placed previously outside of the posterior pole) in the study eye 6. History of DME or DR treatment with macular laser within 3 months prior to screening, or intraocular injections of medication within 6 months prior to screening, and no more than 4 prior intraocular injections in the study eye at any time in the past 7. Patients treated with Monoamine Oxidase B (MAO-B) inhibitors (see Section 4.2.2.1) at the time or up to 3 months prior to randomization or planned initiation during the trial 8. Current or planned, during the trial, use of medications known to be toxic to the retina, lens or optic nerve, or cause vision loss Further criteria apply. |
1. Enfermedad ocular adicional en el ojo del ensayo que, en opinión del investigador, pueda comprometer o alterar la agudeza visual durante el curso del ensayo (por ejemplo: oclusión venosa, presión intraocular no controlada (PIO) > 24mmHg con tratamiento médico óptimo, glaucoma con pérdida de campo visual, uveitis u otra enfermedad inflamatoria ocular, tracción vitreomacular, visión monocular, historial de neuropatía óptica isquémica, o desórdes genéticos cómo retinitis pigmentosa) 2. Edema macular diabético de predominio central (EMD-PC) en el examen clínico y grosor del subcampo central de OCT superior a 300 μm en el ojo del ensayo, medido por Optovue OCT 3. Anomalías del segmento anterior y en el vítreo en el ojo del ensayo que cpuedieran comprometer la evaluación adecuada de la mejor agudeza visual corregida o la exploración adecuada del polo posterior 4. Evidencias de neovascularización en la exploración clínica incluyendo neovascularización activa del iris (pequeñas tramas en el iris no se excluyen) o neovascularización angular en el ojo del ensayo, descartado por gonioscopia (documentada en las 4 semanas antes del sceening o llevada a cabo durante el screening) 5. Fotocoagulación pan-retinal previa (definida como ≥ 100 quemaduras situadas previamente fuera del polo posterior) en el ojo del estudio 6. Historial de tratamiento para EMD o RD con láser macular en los 3 meses anteriores al screening, o inyecciones intraoculares de medicación en los 6 meses anteriores al screening, y no más de 4 inyecciones intraoculares previas en el ojo del estudio en cualquier momento del pasado 7. Pacientes tratados con inihibidores de la Monoamino Oxidasa B (MAO-B) (ver sección 4.2.2.1) en el momento o hasta 3 meses antes de la aleatorización o inicio planeado durante el ensayo 8. Uso actual o planeado, durant el ensayo, de medicación conocida por ser tóxica para la retina , cristalino o nervio óptico, o por causar pérdida de visión Más criterios aplican. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) proportion of patients with any ocular adverse events (according to Common Terminology Criteria for Adverse Events (CTCAE) |
1) proporción de pacientes con cualquier acontecimiento adverso ocular (según los criterios comunes de termonología para acontecimientos adversos (CTCAE) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1) 24 weeks |
1) 24 semanas |
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E.5.2 | Secondary end point(s) |
1) Proportion of patients with at least 2 steps improvement in the study eye on the DRSS at week 12 compared to baseline. 2) The proportion of patients with adverse events other than ocular adverse events over the on treatment period (over 24 weeks) (according to CTCAE). |
1) Proporción de pacientes con al menos 2 pasos de mejoría en el ojo del ensayo en la DRSS a la semana 12 comparado con el inicio inicial (baseline) 2) La proporción de pacientes con acontecimientos adversos diferentes a acontecimientos adversos oculares durante el periodo en tratamiento (más de 24 semanas) (según CTCAE). |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) 12 weeks 2) 24 weeks |
1) 12 semanas 2) 24 semanas |
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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 | 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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 15 |
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 |
Greece |
Italy |
Norway |
Spain |
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
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LVLS |
Última visita del último paciente |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 3 |