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 |
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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 |
The main objectives of the trial are to demonstrate the effectiveness of BI 685509 and to characterize the dose-response relationship for BI 685509 in patients with DKD by assessing 3 doses and placebo. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed and dated written informed consent in accordance with ICH-GCP and local legislation prior to admission to the trial. 2. Male or female patients aged ≥ 18 years at time of consent. 3. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formula) ≥ 20 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory analysis. eGFR must remain ≥ 20 mL/min/1.73 m2 after Visit 1 up to the start of Visit 3, measured by central or any local laboratory analysis. 4. UACR ≥ 200 and < 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1. 5. Treatment with the highest tolerated dose of either ACEi or ARB (but not both together), and stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial. 6. If the patient is taking any of the following medications they should be on a stable dose at least 4 weeks prior to visit 1 until start of treatment, with no planned change of the therapy during the trial: anti- hypertensives, NSAIDs, endothelin receptor antagonists, systemic steroids or SGLT2 inhibitors. 7. Patients with stable type 1 or type 2 diabetes mellitus, diagnosed before informed consent. Treatment (including SGLT2 inhibitor and/or GLP1 receptor agonist) should have been unchanged or changes deemed minor (according to investigator’s judgement) within 4 weeks before Visit 1 and until start of trial treatment. 8. Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the central laboratory. 9. Seated SBP ≥ 110 and ≤ 160 mmHg and DBP ≥ 65 and ≤ 110 mmHg at Visit 1 and optimized anti-hypertensive treatment according to local standard of care and investigator’s judgement. 10. Body Mass Index (BMI) ≥ 18.5 and < 50 kg/m2 at Visit 1. 11. Male patients able to father a child must be willing to use condoms if their sexual partner is a Women of child-bearing potential (WOCBP). WOCBP must be ready and able to use highly effective methods of birth control per ICH M3 (R2). Such methods should be used throughout the trial. |
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E.4 | Principal exclusion criteria |
1. Treatment with Renin Angiotensin Aldosterone System (RAAS) interventions (apart from either ACEi or ARB), phosphodiesterase-5 inhibitors, non-specific phosphodiesterase inhibitors (such as dipyridamole and theophylline), NO donors including nitrates, sGC-stimulators/activators (other than trial treatment) or any other restricted medication (including OATP1B1/3 inhibitors, UGT inhibitors/inducers) as provided in the Investigator Site File (ISF) within 4 weeks prior to visit 1 and throughout screening and baseline run-in. Patients who must or wish to continue the intake of restricted medications (see section 4.2.2.1) or any drug considered likely to interfere with the safe conduct of the trial are also excluded. 2. Any clinically relevant laboratory value from screening until start of trial treatment, which in the investigator’s judgement puts the patient at additional risk. 3. Biopsy or otherwise confirmed non-diabetic chronic kidney disease, or non-diabetic chronic kidney disease in the opinion of investigator, e.g., Autosomal Dominant Polycystic Kidney Disease (ADPKD), uncontrolled lupus nephritis. The presence of a hypertensive etiology does not need to be excluded unless it is evident this is the only cause for the CKD. 4. Any immunosuppression therapy or immunotherapy in the last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent). 5. Acute kidney injury (AKI) according to the Kidney Disease: Improving Global Outcomes (KDIGO) definition in the 30 days prior to Visit 1 until the start of trial treatment. 6. Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment. 7. Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment. 8. The patient has an active infection with SARS-CoV-2 (or is known to have a positive test) from screening until randomisation. 9. Medical history of cancer or treatment for cancer in the last two years prior to Visit 1 (except appropriately treated basal cell carcinoma of the skin, in situ carcinoma of uterine cervix, and prostatic cancer of low grade [T1 or T2]). 10. Major surgery (investigator’s judgement) planned during the trial. 11. History of clinically relevant allergy/ hypersensitivity that would interfere with trial participation including allergy to investigational product/ placebo or its excipients (see Investigator Brochure) 12. Any other medical condition that in the investigator’s opinion poses a safety risk for the patient or may interfere with the trial objectives. 13. Previous randomisation in this trial. Further criteria apply. [...] 17. QTcF-interval > 450 ms in men or > 470 ms in women at any time from screening (Visit 1) until start of treatment. 18. A family history of long QT syndrome. 19. Concomitant use of therapies with a known risk of Torsade de Pointes at screening (Visit 1) and throughout screening and baseline run-in or planned initiation of such therapies during the trial (refer to Section 4.2.2.1). |
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E.5 End points |
E.5.1 | Primary end point(s) |
1) Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1) Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment. 2) Proportion of patients achieving UACR decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment. 3) Proportion of patients achieving UACR decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment.
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1) after 20 weeks 2) after 20 weeks 3) after 20 weeks
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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 | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
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 | 6 |
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 | 26 |
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 |
Argentina |
Australia |
Canada |
China |
Hong Kong |
Japan |
Malaysia |
Mexico |
New Zealand |
United States |
Poland |
Netherlands |
Spain |
Denmark |
Portugal |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
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 | 7 |
E.8.9.2 | In all countries concerned by the trial days | 1 |