E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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. |
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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 | 18.1 |
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 |
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. |
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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
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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 ≥ 25 and < 75 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% (< 97 mmol/mol) 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, non-insulin 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. If the subject has been subjected to specific dietary interventions
then this has to be stable over the past 3 months prior to screening visit.
8. Subject's UACR is ≥ 200 and ≤ 3000 mg/g in a FMV sample at screening and the geometric mean UACR of all FMV samples at visit 4 and at visit 5 is ≥ 200 and ≤ 3000 mg/g, AND the UACR in at least 3 FMV samples at visit 4 and visit 5 is ≥ 200 mg/g.
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E.4 | Principal exclusion criteria |
1. Subject is on, or previously received, renal replacement therapy (e.g. dialysis or kidney transplantation).
2. Subject has significant 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 sitting systolic blood pressure (SBP) <90 or >160 mmHg and/or a diastolic blood pressure (DBP) >90 mmHg at screening.
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E.5 End points |
E.5.1 | Primary end point(s) |
Mean change of log transformed UACR from baseline to end of treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
As per schedule of assessments described in the protocol. |
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E.5.2 | Secondary end point(s) |
• 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
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
As per schedule of assessments described in the protocol. |
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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 | 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 | 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 | 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 | 5 |
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
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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 | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |