E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 Chronic kidney disease |
Diabetes Mellitus, Tipo 2 Enfermedad renal crónica |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes Chronic kidney disease |
Diabetes tipo 2 Enfermedad renal crónica |
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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 | 21.1 |
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.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10064848 |
E.1.2 | Term | Chronic kidney disease |
E.1.2 | System Organ Class | 10038359 - Renal and urinary 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 investigate the effect of once-weekly (OW) semaglutide administered subcutaneously (under the skin, s.c.) versus placebo on renal inflammation and haemodynamics, as measured by magnetic resonance imaging (MRI) in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). |
Investigar el efecto de semaglutida administrada subcutaneamente (bajo la piel, SC) una vez a la semana (1 vez/sem) comparado con un placebo sobre la inflamación renal y la hemodinamia, determinada mediante resonancia magnética (RM), en pacientes con diabetes tipo 2 (DT2) y enfermedad renal crónica (ERC). |
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E.2.2 | Secondary objectives of the trial |
To investigate the effect of OW semaglutide s.c. versus placebo on renal oxidative stress, natriuresis, albumin excretion and kidney function in subjects with T2D and CKD. |
Investigar el efecto de la semaglutida SC 1 vez/sem comparada con un placebo sobre el estrés oxidativo renal, la natriuresis, la excreción de albúmina y la función renal en sujetos con DT2 y ERC. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Male or female - Age 18 years or older at the time of signing informed consent. - Diagnosed with T2D at least 180 days prior to the day of screening. - Glycosylated haemoglobin (HbA1c) equal to or below 9.0% (equal to or below 75 mmol/mol). - Serum creatinine-based estimated glomerular filtration rate (eGFR) equal to or above 40 and equal to or below 75 mL/min/1.73 m^2 (Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)). - Urine albumin-to-creatinine ratio (UACR) equal to or above 30 and below 5000 mg/g. - Treatment with maximum labelled or tolerated dose of a renin-angiotensin-aldosterone system (RAAS) blocking agent including an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB). Treatment dose must be stable for at least 28 days prior to screening. |
-Varón o mujer -De 18 o más años de edad en el momento de firmar el consentimiento informado -Diagnóstico de DT2 al menos 180 días antes del día de la selección. -HbA1c menor o igual a 9,0% (menor o igual a 75 mmol/mol). -Tasa de filtración glomerular basada en la creatinina sérica mayor o igual a 40 y menor o igual a 75 ml/min/1,73 m2 (CKD-EPI). -UACR (relación albúmina-creatinina en orina) mayor o igual a 30 y menor a 5000 mg/g. -Tratamiento con la dosis máxima según ficha técnica o dosis tolerada de un bloqueante del sistema renina-angiotensina-aldosterona (SRAA), como un inhibidor de la enzima convertidora de angiotensina (IECA) o un antagonista de los receptores de angiotensina II (ARA). La dosis de tratamiento deberá mantenerse estable durante al menos 28 días antes de la selección. |
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E.4 | Principal exclusion criteria |
- Use of any glucagon-like peptide 1 receptor agonist (GLP-1 RA) within 30 days prior to screening. -A prior solid organ transplant or awaiting solid organ transplant. -Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening. -Presence or history of malignant neoplasms (other than basal or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) within 5 years prior to the day of screening. -Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations. -Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a fundus examination performed within the past 90 days prior to screening or in the period between screening and V2. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination. -Treatment with systemic anti-inflammatory or immunosuppressant drugs within 90 days prior to screening. Stable treatment with acetylsalicylic acid for prevention of cardiovascular events and occasional use of propionic acid derivatives drugs (e.g. ibuprofen) is allowed. • Any contraindication for MRI according to standard checklist used in clinical routine, including claustrophobia or metallic foreign bodies, metallic implants, internal electrical devices, or permanent makeup/tattoos that cannot be declared magnetic resonance (MR) compatible. • Combination use of an ACE inhibitor and an ARB. |
-Uso de cualquier agonista del receptor del péptido glucagonoide 1 (AR GLP-1) en los 30 días previos a la selección. -Trasplante de órgano sólido previo o en espera de un trasplante de órgano sólido. -Infarto de miocardio, ictus u hospitalización por angina de pecho inestable o accidente isquémico transitorio en los 180 días previos al día de la selección. -Presencia o antecedentes de neoplasia maligna (distinta de cáncer de células basales o escamosas de piel, carcinoma in situ del cuello uterino o cáncer de próstata in situ) en los 5 años previos al día de la selección. -Enfermedades renales congénitas o hereditarias como poliquistosis renal, enfermedad renal autoinmunitaria, incluida glomerulonefritis, o malformaciones congénitas de las vías urinarias. -Retinopatía o maculopatía diabética no controlada y potencialmente inestable, verificada mediante exploración del fondo de ojo realizada en los 90 días previos a la selección o en el período comprendido entre la selección y la V2. La midriasis farmacológica es un requisito a menos que se utilice una cámara fotográfica digital del fondo de ojo especificada para exploración sin midriasis. -Tratamiento con antiinflamatorios sistémicos o inmunodepresores en los 90 días previos a la selección. Se permite el tratamiento estable con ácido acetilsalicílico para la prevención de episodios cardiovasculares y el uso ocasional de derivados del ácido propiónico (p. ej., ibuprofeno). • Cualquier contraindicación para la RM según la lista de comprobación de uso habitual en la práctica clínica, incluidos claustrofobia o cuerpos extraños metálicos, implantes metálicos, dispositivos eléctricos internos o maquillaje permanente o tatuajes que no puedan declararse compatibles con la RM. • Uso combinado de un IECA y un ARA. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in kidney oxygenation (cortex), blood oxygenation-level dependent magnetic resonance imaging (BOLD MRI) (R2*) 2. Change in kidney oxygenation (medulla), BOLD MRI (R2*) 3. Change in global kidney perfusion (MRI) 4. Change in kidney inflammation (cortex), longitudinal relaxation time (T1) mapping (MRI) 5. Change in kidney inflammation (medulla), T1 mapping (MRI) |
1. Cambio de la oxigenación renal (corteza), imagen de resonancia magnética dependiente del nivel de oxígeno en sangre (RM BOLD) (R2*) 2. Cambio de la oxigenación renal (médula), RM BOLD (R2*) 3. Cambio de la perfusión renal global (RM) 4. Cambio de la inflamación renal (corteza), tiempo de relajación longitudinal mapeo T1 (RM) 5. Cambio de la inflamación renal (médula), mapeo T1 (RM) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. - 5. From baseline (week 0) to end of treatment (week 52) |
1.- 5 Desde el momento basal (semana 0) al final del tratamiento (semana 52) |
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E.5.2 | Secondary end point(s) |
1. Change in gene expression assessed by single nucleus ribonucleic acid (RNA) sequencing (kidney biopsy) 2. Change in glomerular basement membrane width (kidney biopsy) 3. Change in apparent diffusion coefficient (ADC) (cortex) (MRI) 4. Change in ADC (medulla) (MRI) 5. Change in mean renal artery resistive index (RARI) (MRI) 6. Change in mean arterial flow (MRI) 7. Change in natriuresis (urinary sodium excretion) (urinalysis) 8. Change in albumin excretion rate (urinalysis) 9. Change in kidney function (creatinine clearance) (urinalysis) |
1. Cambio de la expresión génica valorada por secuenciación del ARN de un solo núcleo (biopsia renal) 2. Cambio del ancho de la membrana basal glomerular (biopsia renal) 3. Cambio del coeficiente de difusión aparente (CDA) (corteza) (RM) 4. Cambio del CDA (médula) (RM) 5. Cambio en el índice de resistencia medio de la arteria renal (IRAR) 6. Cambio en el flujo arterial medio (RM) 7. Cambio de la natriuresis (excreción urinaria de sodio) (análisis de orina) 8. Cambio de la tasa de excreción de albúmina (análisis de orina) 9. Cambio de la función renal (aclaramiento de creatinina) (análisis de orina) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. - 9. From baseline (week 0) to end of treatment (week 52) |
1. - 9. Desde el momento basal (semana 0) al final del tratamiento (semana 52) |
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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 | No |
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 | 3 |
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 |
Canada |
South Africa |
United States |
European Union |
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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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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 | 2 |
E.8.9.1 | In the Member State concerned days | 23 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 23 |