E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Diabetic nephropathy |
Nefropatia diabetica |
|
E.1.1.1 | Medical condition in easily understood language |
Diabetic nephropathy is chronic kidney disease or damage that can occur in people with diabetes mellitus. |
La nefropatia diabetica è una patologia renale cronica o un danno renale che può insorgere in persone con diabete mellito |
|
E.1.1.2 | Therapeutic area | Not possible to specify |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
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 |
|
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 evaluate the efficacy of ASP8232 in reducing Urinary Albumin to Creatinine Ratio (UACR) in subjects with Type 2 Diabetes Mellitus (T2DM) and Chronic Kidney Disease (CKD) at 12 weeks compared to placebo. |
Valutare l’efficacia di ASP8232 nel ridurre il rapporto urinario albumina/creatinina (Urinary Albumin Creatinine Ratio, UACR) in soggetti con diabete mellito di tipo 2 (Type 2 Diabetes Mellitus, T2DM) e malattia renale cronica (Chronic Kidney Disease, CKD) a 12 settimane rispetto al placebo |
|
E.2.2 | Secondary objectives of the trial |
1. To evaluate the efficacy of ASP8232 in reducing the 24h urinary albumin excretion rate (AER) in patients with T2DM and CKD at 12 weeks compared to placebo
2. To evaluate the safety and tolerability of ASP8232 in patients with T2DM and CKD
3. To evaluate the pharmacokinetics (PK) of ASP8232 in patients with T2DM and CKD
4. To evaluate pharmacodynamics (PD) of ASP8232 by assessing vascular adhesion protein-1 (VAP-1) plasma concentration and inhibition of VAP-1 activity and total antioxidant status (TAS) in serum
|
1. Valutare l’efficacia di ASP8232 nel ridurre il tasso di escrezione dell’albumina urinaria (urinary albumin excretion rate, AER)
delle 24 ore in pazienti con T2DM e CKD a 12 settimane rispetto al placebo
2. Valutare l’efficacia e la tollerabilità di ASP8232
3. Valutare la farmacocinetica (pharmacokinetics, PK) di ASP8232
4. Valutare la farmacodinamica (pharmacodynamics, PD) di ASP8232 misurando la concentrazione plasmatica di proteina 1 di
adesione vascolare (vascular adhesion protein-1, VAP-1) e l’inibizione dell’attività di VAP-1 e lo stato totale degli antiossidanti
(TAS) nel siero |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female subject who is > 18 and < 85 years of age.
2. Subject must have a eGFR (based on the CKD-EPI equation) at screening of ≥ 30 and < 60 mL/min/1.73m2.
3. Subject must have a documented diagnosis of T2DM and received anti-diabetic medication (oral and/or insulin) for at least one year prior to screening.
4. Subject’s HbA1c level is < 11.0% at screening.
5. Subject is on a stable therapy with an ACE inhibitor or ARB for at least three months prior to screening.
6. Subject who receives anti-hypertensive treatment, oral anti-diabetic agents and/or vitamin D receptor activators at screening needs to be on stable therapy for at least three months prior to screening.
7. Subject’s UACR is ≥ 200 and ≤ 3000 mg/g at screening.
|
1. Soggetti maschi o femmine di età >18 e <85 anni.
2. Il soggetto deve avere un eGFR (basato sull’equazione CKD-EPI) allo screening ≥30 e <60 ml/min/1,73 m2.
3. Il soggetto deve avere una diagnosi documentata di T2DM e deve aver ricevuto un farmaco antidiabetico (per via orale e/o
insulina) per almeno un anno prima dello screening.
4. Il livello di HbA1c del soggetto è <11,0% (<97 mmol/mol) allo screening.
5. Il soggetto è in terapia stabile con un ACE inibitore o ARB da almeno tre mesi prima dello screening.
6. Il soggetto che riceve trattamento anti-ipertensivo, agenti antidiabetici per via orale e/o attivatori del recettore della vitamina
D allo screening deve essere in terapia stabile da almeno tre mesi prima dello screening.
7. L’UACR del soggetto è ≥200 e ≤3000 mg/g allo screening |
|
E.4 | Principal exclusion criteria |
1. Subject is on, or previously received, renal replacement therapy (e.g. dialysis or kidney transplantation).
2. Subject has obstructive uropathy or other causes of renal impairment not related to parenchymal renal disorder and/or disease of the kidney; or subject currently has or has had in the past renal disease secondary to malignancy.
3. Subject’s renal impairment and/or albuminuria is considered to be of other origin than Diabetic Kidney Disease
4. Subject has known (auto-) immune disorder and/or received immunosuppression for more than two weeks, cumulatively, within 12 weeks prior to screening or anticipated need for immuno-suppressive therapy during the study
5. Subject has active urinary tract infection which requires treatment or clinically significant infection at the time of screening or randomization
6. Subject is diagnosed with type 1 diabetes mellitus or diabetes mellitus with unclear etiology.
7. Subject has a supine systolic blood pressure (SBP) <90 or >160 mmHg and/or a diastolic blood pressure (DBP) >90 mmHg at screening.
|
1. Il soggetto è, o è stato precedentemente, in terapia di sostituzione renale (per esempio dialisi o trapianto di rene).
2. Il soggetto presenta uropatia ostruttiva oppure altre cause di insufficienza renale non legate a malattia renale parenchimale
e/o a malattia renale; oppure il soggetto attualmente ha, o ha avuto in passato, malattia renale secondaria a malignità.
3. L’insufficienza renale del soggetto e/o l’albuminuria è ritenuta di altra origine piuttosto che malattia renale diabetica.
4. Il soggetto è affetto da conosciuto un disturbo (auto-)immunitario conosciuto e/o ha ricevuto immunosoppressione per più di
due settimane, complessivamente, entro le 12 settimane precedenti lo screening oppure ha avuto necessità anticipata di
terapia immunosoppressiva durante lo studio.
5. Il soggetto ha un’infezione attiva del tratto urinario che richiede trattamento oppure un’infezione clinicamente significativa al
momento dello screening o della randomizzazione.
6. Al soggetto è stato diagnosticato diabete mellito di tipo 1 oppure diabete mellito di eziologia incerta.
7. Il soggetto ha una pressione sanguigna sistolica (systolic blood pressure, SBP) da seduto <90 o >160 mmHg e/o pressione
sanguigna diastolica (diastolic blood pressure, DBP) >90 mmHg allo screening. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Mean change of log transformed UACR from baseline to end of treatment. |
Cambiamento medio dell’UACR log-trasformato dal valore basale alla fine del trattamento |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
As per schedule of assessments described in the protocol. |
Come da programma delle valutazioni descritto nel protocollo |
|
E.5.2 | Secondary end point(s) |
• Mean change of log transformed UACR over time of treatment using the repeated measurements method from baseline to end of treatment.
• The proportion of subjects with >30%/40%/50% reduction in UACR from baseline to end of treatment
• Mean change of log transformed AER from baseline to end of treatment
• The proportion of subjects with >30%/40%/50% reduction in AER from baseline to end of treatment
|
• Analisi delle misure ripetute dal valore basale alla fine del trattamento
• Percentuale dei soggetti con riduzione in UACR >30%/40%/50% dal valore basale alla fine del trattamento
• Cambiamento medio del tasso di escrezione dell’albumina (AER) log-trasformato dal valore basale alla fine del trattamento
• La percentuale di soggetti con riduzione nel tasso di escrezione dell’albumina (AER) >30/40/50% dal valore basale alla fine del
trattamento
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
As per schedule of assessments described in the protocol. |
Come da programma delle valutazioni descritto nel protocollo |
|
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 | No |
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 | 1 |
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 | 13 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 80 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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
|
|
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 | 3 |
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 | 0 |