E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
Diabete mellito di tipo 2 e nefropatia diabetica |
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E.1.1.1 | Medical condition in easily understood language |
Type II Diabetes Mellitus and Diabetic Kidney Disease |
Diabete mellito di tipo 2 e nefropatia diabetica |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10061835 |
E.1.2 | Term | Diabetic nephropathy |
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 |
Demonstrate whether, in addition to standard of care (SoC), finerenone is superior to placebo in delaying the progression of kidney disease, as measured by the composite endpoint of time to first occurrence of kidney failure, a sustained decrease of eGFR = 40% from baseline over at least 4 weeks or renal death |
¿ Dimostrare se, in aggiunta alla terapia standard (SoC), finerenone sia superiore al placebo nel ritardare la progressione della malattia renale, valutata in base all¿endpoint composito del tempo alla prima comparsa dell¿insufficienza renale, riduzione importante di eGFR = 40% dal basale per almeno 4 settimaneo morte renale |
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E.2.2 | Secondary objectives of the trial |
Determine whether, in addition to SoC, finerenone compared to placebo:¿ Delays the time to first occurrence of the following composite endpoint: cardiovascular (CV) death or non-fatal CV events (i.e. non fatalmyocardial infarction, non-fatal stroke, hospitalization for heart failure [HF])¿ Delays the time to all-cause mortality¿ Delays the time to all-cause hospitalizations¿ Change in UACR from baseline to Month 4¿ Delays the time to first occurrence of the following composite endpoint:onset of kidney failure, a sustained decrease in eGFR of =57% from baseline over at least 4 weeks or renal death. |
Gli obiettivi secondari di questo studio sono quelli di stabilire se, in aggiunta al SoC, finerenone confrontato a placebo sia in grado di: ¿ prolungare il tempo alla prima comparsa del seguente endpoint composito: morte cardiovascolare (CV) o eventi CV non-fatali (cio¿ infarto miocardico non fatale, ictus non fatale, ospedalizzazione per scompenso cardiaco [HF]) ¿ Ritardare il tempo alla mortalit¿ per tutte le cause ¿ Ritardare il tempo all¿ospedalizzazione per tutte le cause ¿ Determinare variazioni dell¿UACR dal basale al mese 4 ¿ Ritardare il tempo alla prima comparsa del seguente endpoint composito: comparsa di insufficienza renale, riduzione importante di eGFR di =57% dal basale per almeno 4 settimane o morte renale
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Men or women aged 18 years and older. The lower age limit may be higher if legally required in the participating country.- Women of childbearing potential can only be included in the study if a pregnancy test is negative at the Screening Visit and if they agree to use adequate contraception. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g. condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate) or 6 months of spontaneous amenorrhea with serum FSH levels > 40 mIU/mL [for US only: FSH levels > 40 mIU/mL and estradiol < 20 pg/mL] or have had surgical treatment such as bilateral tubal ligation, bilateral ovarectomy, or hysterectomy.- Subjects with type 2 diabetes mellitus as defined by the American Diabetes Association - Subjects with a clinical diagnosis of DKD based on either of the following criteria at the Run-in and Screening Visit:• Persistent high albuminuria defined as UACR of = 30 mg/g ( = 3.4 mg/mmol) but < 300 mg/g (< 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR = 25 but < 60 mL/min/1.73 m2 and presence of diabetic retinopathy in the medical history OR• Persistent very high albuminuria defined as UACR of = 300 mg/g (= 33.9 mg/mmol) in 2 out of 3 first morning void samples and eGFR = 25 but < 75 mL/min/1.73 m2 - Prior treatment with ACEIs and ARBs as follows:• For at least 4 weeks prior to the Run-in Visit, subjects should be treated with either an ACEI or ARB, or both• Starting with the Run in Visit, subjects should be treated with only an ACEI or ARB• For at least 4 weeks prior to the Screening Visit, subjects should be treated with the maximum tolerated labeled dose (but not below the minimal labeled dose) of only an ACEI or an ARB (not both) preferably without any adjustments to dose or choice of agent or to any other antihypertensive or antiglycemic treatment - Serum potassium = 4.8 mmol/L at both the Run-in and the Screening Visit |
• Uomini o donne =18 anni d’età • T2DM secondo la definzione della “American Diabetes Association” • Diagnosi di DKD con almeno uno dei seguenti criteri alle visite di Run-in e di Screening: - albuminuria persistente elevata e presenza di retinopatia diabetica OPPURE - albuminuria persistente molto elevata • Pretrattati per almeno 4 settimane prima della Visita di Screening con ACEI o ARB alla dose massima tollerata indicata sul foglio illustrativo, preferibilmente senza aggiustamenti della dose o scelta di un farmaco o di un altro trattamento • Potassiemia =4.8 mmol/L.
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E.4 | Principal exclusion criteria |
- Known significant non-diabetic renal disease, including clinically relevant renal artery stenosis - HbA1c > 12% (> 108 mmol/mol) at the Run-in Visit or Screening Visit- Uncontrolled arterial hypertension with mean sitting systolic blood pressure (SBP) = 170 mmHg or mean sitting diastolic blood pressure (DBP) = 110 mmHg at the Run in Visit or mean sitting SBP = 160 mmHg or mean sitting DBP = 100 mmHg at the Screening Visit- Subjects with a clinical diagnosis of chronic heart failure with reduced ejection fraction (HFrEF) and persistent symptoms (New York Heart Association class II-IV) at the Run in Visit (class 1A recommendation forMRAs)- Dialysis for acute renal failure within 12 weeks prior to the Run-in Visit- Renal allograft in place or a scheduled kidney transplant within the next 12 months from the Run in Visit |
• Nefropatia non-diabetica confermata significativa, compresa una stenosi dell’arteria renale clinicamente rilevante • Ipertensione arteriosa non controllata (cioè pressione sistolica media in posizione seduta =170 mmHg, pressione diastolica in posizione seduta =110 mmHg alla visita di run-in, oppure pressione sistolica media in posizione seduta =160 mmHg, pressione diastolica in posizione seduta =100 mmHg allo screening) • Diagnosi clinica di HFrEF cronica e sintomi persistenti (classe II-IV secondo la NYHA) alla visita di run-in (classe 1A raccomandazione per MRA) • Dialisi per l’insufficienza renale acuta entro 12 settimane dalla visita di run-in • Trapianto di rene effettuato o programmato entro i prossimi 12 mesi • HbA1c > 12%.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to the first occurrence of the composite endpoint of onset of kidneyfailure, a sustained decrease of eGFR = 40% from baseline over at least 4 weeks and renal death. |
Tempo alla prima comparsa dell’endpoint composito : comparsa di insufficienza renale, riduzione importante di eGFR >40% dal basale per almeno 4 settimane o morte renale |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
From randomization (Visit 1) until the end of study following the study termination decision, approximately from 16 to 40 months |
Dalla randomizzazione (visita 1) a fine studio in base alla decisione sulla conclusione dello studio, circa da 16 a 40 mesi |
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E.5.2 | Secondary end point(s) |
- Time to first occurrence of the following composite endpoint: cardiovascular death or non-fatal cardiovascular events (myocardial infarction, stroke, hospitalization for heart failure)- Time to all-cause mortality- Time to all-cause hospitalizations- Change in UACR from baseline to Month 4*- Time to first occurrence of the following composite endpoint:onset of kidney failure, a sustained decrease in eGFR of =57% from baseline overat least 4 weeks or renal death. |
- Tempo alla rpima comparsa del seguente endpoint composito: morte cardiovascolare o eventi cardiovascolari non fatali (infarto del miocardio, stroke, ospedalizzazione per insufficienza cardiaca)- Tempo alla mortalit¿ per qualunque causa Tempo all'ospedalizzazione per qualunque causa Cambiamento in UACR da basale al mese 4* Tempo alla prima comparsa del seguente endpoint composito: comparsa di insufficienza renale, diminuzione sostenuta di eGFR =57% dal basale ad almeno 4 settimane o morte renale. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
For all endpoints:From randomization (Visit 1) until the end of study following the study termination decision, approximately from 16 to 40 monthsExcept *At baseline / randomization (Visit 1) and Month 4 |
Per tutti gli endpoint: Dalla randomizzaeione (Visita 1) fino a fine studio secondo la decisione di conclusione dello studio circa da 16 a 40 mesi Tranne *Al basale / randomizzazione (Visita 1) e Mese 4 |
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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 | 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 | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 300 |
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 |
Chile |
China |
Colombia |
Hong Kong |
Israel |
Japan |
Korea, Republic of |
New Zealand |
Philippines |
Russian Federation |
Saudi Arabia |
Singapore |
South Africa |
Taiwan |
Thailand |
Turkey |
Ukraine |
United States |
Vietnam |
Austria |
Belgium |
Bulgaria |
Finland |
France |
Germany |
Greece |
Italy |
Lithuania |
Netherlands |
Norway |
Poland |
Portugal |
Spain |
Sweden |
Switzerland |
United Kingdom |
Czechia |
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 | 0 |
E.8.9.1 | In the Member State concerned months | 39 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 39 |
E.8.9.2 | In all countries concerned by the trial days | 0 |