E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 |
Diabetes Mellitus tipo 2 |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes |
Diabetes tipo 2 |
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E.1.1.2 | Therapeutic area | Diseases [C] - Nutritional and Metabolic Diseases [C18] |
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 | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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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 primary objective is to assess the long-term effects of treatment with semaglutide compared to placebo, both added to standard-of-care, on diabetic retinopathy development and progression in subjects with T2D |
El objetivo principal es evaluar los efectos a largo plazo del tratamiento con semaglutida en comparación con placebo, ambos añadidos al tratamiento de referencia, sobre la aparición y la progresión de la retinopatía diabética en sujetos con DT2. |
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E.2.2 | Secondary objectives of the trial |
The secondary objectives are to assess the effects of treatment with semaglutide compared to placebo, both added to standard-of-care, with regards to: - Visual acuity - Diabetic retinopathy manifestations (occurrence of diabetic macular oedema or proliferative diabetic retinopathy) - Diabetic retinopathy treatments (laser photocoagulation, intravitreal agents and vitrectomy) - Modifiable risk factors for diabetic retinopathy (glycaemia, blood pressure and lipids). |
Los objetivos secundarios fundamentales son evaluar los efectos del tratamiento con semaglutida en comparación con placebo, ambos añadidos al tratamiento de referencia, en lo que respecta a: - agudeza visual - manifestaciones de retinopatía diabética (ocurrencia de edema macular diabetico o retinopatía diabética proliferativa) - tratamientos de la retinopatía diabética (fotocoagulación laser, vitrectomía y agentes intravítreos) -factores de riesgo modificables por la retinopatía (glucemia, presión arterial y lípidos). |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female, age equal to or above18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus at least10 years prior to the day of screening. - HbA1c of 7.0-10.0% (53-86 mmol/mol) (both inclusive). Eye inclusion criteria (both eyes must meet the following criteria): - ETDRS level of 10-75 (both inclusive) evaluated by fundus photography and confirmed by central reading centre. - No ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema twelve months prior to the day of screening. - No anticipated need for ocular or intraocular treatment for diabetic retinopathy or diabetic macular oedema within six months after randomisation. - Best-corrected visual acuity equal to or above 30 letters using the ETDRS visual acuity protocol. - No previous treatment with pan-retinal laser photocoagulation. - No substantial non-diabetic ocular condition that, in the opinion of the ophthalmologist, would impact diabetic retinopathy or diabetic macular oedema progression during the trial. - No substantial media opacities that would preclude successful imaging. |
•Pacientes de ambos sexos, de 18 años o más en el momento de la firma del consentimiento informado. •Diagnóstico de diabetes mellitus tipo 2 ≥ 10 años antes del día de la selección. •HbA1c de 7,0%-10,0 % (53-86 mmol/mol) (ambos inclusive). Criterios de inclusión oculares (ambos ojos deben cumplir los criterios siguientes) •Nivel ETDRS de 10-75 (ambos inclusive) evaluado mediante fotografía del fondo de ojo y confirmado por el centro de interpretación centralizada. •Ausencia de tratamiento ocular o intraocular para la retinopatía diabética o el edema macular diabético doce meses antes del día de la selección. •Ausencia de necesidad prevista de tratamiento ocular o intraocular por retinopatía diabética o edema macular diabético en los seis meses siguientes a la aleatorización. •Mejor agudeza visual corregida ≥ 30 letras según el protocolo de agudeza visual del ETDRS. •Ausencia de tratamiento previo con fotocoagulación panretiniana con láser. •Ausencia de trastornos oculares no diabéticos importantes que, en opinión del oftalmólogo, afectarían a la evolución de la retinopatía diabética o el edema macular diabético durante el ensayo. •Ausencia de opacidades importantes de los medios oculares que impedirían obtener imágenes satisfactorias. |
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E.4 | Principal exclusion criteria |
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris or transient ischaemic attack within the past 60 days prior to the day of screening. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening. - Subjects presently classified as being in New York Heart Association (NYHA) Class IV. - Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR below 30 ml/min/1.73 m2 (Based on medical history using latest available and no more than 6 months old assessment. If not available in medical records a local laboratory measurement must be made available before randomisation). - Personal or first degree relative(s) history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. - Presence or history of malignant neoplasms within the past 5 years prior to the day of screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed. - Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using highly effective contraceptive methods. - Current or previous (within 30 days before screening) treatment with any GLP-1 receptor agonist or DPP-4 inhibitor. - Receipt of any investigational medicinal product within 30 days before screening. - Previous participation in this trial. Participation is defined as randomisation. - Known or suspected hypersensitivity to trial products or related products. - Any disorder, which in the investigator’s opinion might jeopardise subject’s safety or compliance with the protocol. |
- cualquiera de los siguientes: infarto de miocario, ictus, hospitalización por angina pectoris inestable o ataque isquémico transitorio en los 60 días previos al día de la selección. - Revascularización arterial periférica , carótida o coronaria planeada conocida el día de la selección. - Subjects presently classified as being in New York Heart Association (NYHA) Class IV. - Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of eGFR below 30 ml/min/1.73 m2 (Based on medical history using latest available and no more than 6 months old assessment. If not available in medical records a local laboratory measurement must be made available before randomisation). |
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E.5 End points |
E.5.1 | Primary end point(s) |
Presence of 3 or more steps ETDRS (Early Treatment Diabetic Retinopathy Study) subject level progression |
la presencia de progresión en cada sujeto de ≥ 3 grados en la escala ETDRS (Early Treatment Diabetic Retinopathy Study) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Time to first 3 or more steps ETDRS subject level progression or central involved diabetic macular oedema (ciDME) in either eye 2. Change from baseline in visual acuity 3. Occurrence of treatment for diabetic retinopathy or diabetic macular oedema |
1.Tiempo transcurrido entre la aleatorización y la primera progresión de ≥ 3 grados en la escala ETDRS en cada sujeto o el edema macular diabético con afectación central (EMDac) en cualquier ojo.
2.variaciones de la agudeza visual desde el momento basal 3.aparición de tratamiento para la retinopatía diabética o el edema macular diabético. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. From randomisation to event 2. + 3. At year 5 |
1. Desde la randomización hasta el evento 2. + 3. en el año 5 |
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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) | 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) | 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 | 62 |
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 |
Brazil |
Canada |
European Union |
India |
Israel |
Mexico |
Russian Federation |
Serbia |
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 | 6 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 6 |
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 | 13 |