E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetes Mellitus, Type 2 Chronic kidney disease |
Diabete Mellito di tipo 2 Patologia renale cronica |
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E.1.1.1 | Medical condition in easily understood language |
Type 2 diabetes Chronic kidney disease |
Diabete di tipo 2 Malattia renale cronica |
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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 | 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.1.2 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.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To demonstrate that semaglutide delays the progression of renal impairment and lowers the risk of renal and cardiovascular mortality compared to placebo, both added to standard-of-care, in subjects with type 2 diabetes and chronic kidney disease. |
Dimostrare che semaglutide ritarda la progressione della compromissione renale e riduce il rischio di mortalità renale e cardiovascolare rispetto al placebo, entrambi aggiunti al trattamento standard, in soggetti con diabete di tipo 2 e malattia renale cronica. |
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E.2.2 | Secondary objectives of the trial |
To compare the effect of treatment with semaglutide versus placebo, both added to standard-of-care in subjects with type 2 diabetes and chronic kidney disease with regards to cardiovascular morbidity, peripheral artery disease, glycaemic control, body weight, blood pressure and safety. |
Comparare l'effetto del trattamento con semaglutide versus placebo, entrambi aggiunti alla terapia standard, in soggetti con diabete di tipo 2 e malattia renale cronica per quanto riguarda la morbidità cardiovascolare, malattia delle arterie periferiche, controllo glicemico, peso corporeo, pressione arteriosa e sicurezza. |
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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. Japan 20 years - Diagnosed with type 2 diabetes mellitus - HbA1c (glycated haemoglobin) equal to or below 10% (equal to or below 86 mmol/mol) - Renal impairment defined either by: a) serum creatinine-based eGFR (estimated glomerular filtration rate) equal to or above 50 and equal to or below 75 mL/min/1.73 m^2 (chronic kidney disease - epidemiology collaboration, CKD-EPI) and UACR (urinary albumin-to-creatinine ratio) above 300 and below 5000 mg/g or b) serum creatinine-based eGFR equal to or above 25 and below 50 mL/min/1.73 m^2 (CKDEPI) and UACR above 100 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 an angiotensin II receptor blocker (ARB), unless such treatment is contraindicated or not tolerated. Treatment dose must be stable for at least 4 weeks prior to the date of the laboratory assessments used for determination of the inclusion criteria for renal impairment and kept stable until screening. |
- Soggetti di sesso maschile o femminile, con età pari o superiore a 18 anni al momento della firma del consenso informato. 20 anni per il Giappone - Diagnosi di diabete mellito di tipo 2 - HbA1c (emoglobina glicata) uguale o inferiore al 10% (uguale o inferiore a 86 mmol/mol) - Compromissione renale definita da: a) eGFR basato su creatinina sierica (velocità di filtrazione glomerulare stimata) uguale o superiore a 50 e uguale o inferiore a 75 ml/min/1,73 m^2 (malattia renale cronica - collaborazione epidemiologia, CKD-EPI) e UACR (rapporto tra albumina urinaria e creatinina) superiore a 300 e inferiore a 5000 mg/g o b) eGFR sierico a base di creatinina uguale o superiore a 25 e inferiore a 50 ml/min/1,73 m^2 (CKD-EPI) e UACR superiore a 100 e inferiore a 5000 mg/g - Trattamento con la dose massima approvata o tollerata di un agente bloccante il sistema renina-angiotensina-aldosterone (RAAS) comprendente un inibitore dell'enzima di conversione dell'angiotensina (ACE) o un bloccante del recettore dell'angiotensina II (ARB), a meno che tale trattamento non sia controindicato o non tollerato. La dose di trattamento deve essere stabile per almeno 4 settimane prima della data delle valutazioni di laboratorio utilizzate per la determinazione dei criteri di inclusione per l'insufficienza renale e mantenuta stabile fino allo screening. |
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E.4 | Principal exclusion criteria |
- Congenital or hereditary kidney diseases including polycystic kidney disease, autoimmune kidney diseases including glomerulonephritis or congenital urinary tract malformations - Use of any glucagon-like peptide-1 (GLP-1) receptor agonist within 30 days prior to screening - Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 60 days prior to the day of screening - Presently classified as being in New York Heart Association (NYHA) Class IV heart failure - Planned coronary, carotid or peripheral artery revascularisation - Current (or within 90 days) chronic or intermittent haemodialysis or peritoneal dialysis - 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 randomisation. Pharmacological pupil-dilation is a requirement unless using a digital fundus photography camera specified for non-dilated examination |
- Patologie congenite o ereditarie dei reni, tra cui malattie del rene policistico, malattie renali autoimmuni incluse glomerulonefriti o malformazioni congenite delle vie urinarie - Uso di qualsiasi agonista del recettore del glucagon-like peptide-1 (GLP-1) entro 30 giorni prima dello screening - Infarto miocardico, ictus, ospedalizzazione per angina pectoris instabile o attacco ischemico transitorio entro 60 giorni prima del giorno dello screening - Insufficienza cardiaca di classe IV secondo la classificazione New York Heart Association (NYHA) - Pianificazione di una rivascolarizzazione coronarica, carotidea o dell'arteria periferica - Attuale emodialisi cronica o intermittente o dialisi peritoneale (o entro 90 giorni) - Retinopatia o maculopatia diabetica incontrollata e potenzialmente instabile. Verificato attraverso un esame del fondus oculare effettuato negli ultimi 90 giorni prima dello screening o nel periodo tra lo screening e la randomizzazione. La dilatazione pupillare farmacologica è un requisito a meno che non si utilizzi una fotocamera digitale per il fundus specificata per l'esame non dilatato |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first occurrence of a composite endpoint consisting of: onset of persistent equal to or above 50% reduction in estimated glomerular filtration rate (eGFR) (CKDEPI) compared with baseline, onset of persistent eGFR (CKD-EPI) below 15 mL/min/1.73 m^2, initiation of chronic renal replacement therapy (dialysis or kidney transplantation), renal death, or cardiovascular death. |
Tempo fino alla prima occorrenza di un endpoint composito costituito da: Insorgenza di una persistente riduzione uguale o superiore al 50% del tasso di filtrazione glomerulare stimato (eGFR) (CKDEPI) rispetto al basale; insorgenza di un eGFR (CKD-EPI) persistente inferiore a 15 mL/min/1,73 m^2; inizio di una terapia cronica di sostituzione renale (dialisi o trapianto di rene), morte renale o morte cardiovascolare. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomisation (week 0) to end-of-trial (up to 61 months or more) |
Dalla randomizzazione (settimana 0) alla fine dello studio clinico (fino a 61 mesi o più) |
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E.5.2 | Secondary end point(s) |
1. Annual rate of change in eGFR (CKD-EPI) (total eGFR slope) 2. Time to first occurrence of a composite cardiovascular MACE endpoint consisting of: - Non-fatal myocardial infarction - Non-fatal stroke - CV death 3. Time to occurrence of all-cause death |
1. Tasso annuo di variazione dell'eGFR (CKD-EPI) (riduzione totale dell'eGFR) 2. Tempo fino alla prima occorrenza di un endpoint cardiovascolare composito composto da: - Infarto miocardico non fatale - Ictus non fatale - morte CV 3. Tempo al verificarsi della morte per tutte le cause |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all secondary endpoints: From randomisation (week 0) to end-of-trial (up to 61 months or more) |
Per tuti gli endopints secondari: dalla randomizzazione (settimana 0) alla fine dello studio clinico (fino a 61 mesi o più) |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 119 |
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 | Information not present in EudraCT |
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 |
Australia |
Brazil |
Canada |
China |
India |
Israel |
Japan |
Malaysia |
Mexico |
Russian Federation |
South Africa |
Thailand |
Turkey |
Ukraine |
United States |
European Union |
Argentina |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 18 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 1 |
E.8.9.2 | In all countries concerned by the trial days | 18 |