A study to test whether different doses of BI 690517 alone or incombination with empagliflozin improve kidney function in people withchronic kidney disease

Phase 1

Conditions: chronic kidney disease
MedDRA version: 23.1Level: PTClassification code 10064848Term: Chronic kidney diseaseSystem Organ Class: 10038359 - Renal and urinary disorders
Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Registration Number: EUCTR2021-001434-19-IT

Lead Sponsor: BOEHRINGER-INGELHEIM ITALIA S.P.A.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 552

Inclusion Criteria

1. Signed and dated written informed consent in accordance with ICHGCP
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) = 30 and < 90 mL/min/1.73 m2 at Visit 1 by central laboratory
analysis.
4. UACR = 200 and < 5,000 mg/g in spot urine (midstream urine
sample) by central laboratory analysis at Visit 1.1
5. If the patient is taking any of the following medications they should
be on a stable dose for at least 4 weeks prior to visit 1 and until first
randomisation prior to run-in with no planned change of the therapy
during the trial: anti-hypertensives, NSAIDs, endothelin receptor
antagonists, low dose systemic steroids (e.g. prednisolone =10 mg or
equivalent).
6. Treatment with a clinically appropriate, stable dose of either ACEi or
ARB (but not both together), for = 4 weeks prior to visit 1 and until first
randomisation with no planned change of the therapy during the trial.
7. In the Investigator's opinion, one or more of the following underlying
kidney disease causes:
-- Diabetic kidney disease. These patients must have type 2 diabetes
mellitus and their treatment (including GLP1 receptor agonist) should be
unchanged or changes deemed minor (according to investigator's
judgement) within 4 weeks prior to Visit 1 and until first randomisation.
-- Hypertensive kidney disease
-- Chronic glomerulonephritis defined as one of the following:
o IgA nephropathy,
o Membranous nephropathy
o Focal Segmental Glomerulosclerosis (FSGS)
8. Glycated Haemoglobin (HbA1c) < 10.0% at Visit 1 measured by the
central laboratory.
9. Serum potassium = 4.8 mmol/L at Visit 1 measured by the central
laboratory.
10. Seated SBP = 110 and = 160 mmHg and DBP = 65 and = 110 mmHg
at Visit 1 (mean values from three BP measurements) and optimised
anti-hypertensive treatment according to local standard of care and
investigator's judgement.
11. Body Mass Index (BMI) = 18.5 and < 50 kg/m2 at Visit 1.
12. Women of child-bearing potential2 (WOCBP) must be ready and able
to use highly effective methods of birth control. Such methods should be
used throughout the trial. Men must be vasectomised or willing and able
to use a condom if their partner is a WOCBP.
Additional inclusion criteria to be assessed before second randomisation
(start of Treatment Period):
1. Serum potassium = 4.8 mmol/L measured by local or central
laboratory within 7 days prior to randomisation to the Treatment Period.
2. eGFR (Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]
formula) = 20 mL/min/1.73 m2 measured by local or central laboratory
within 7 days prior to randomisation to the Treatment Period.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 300
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 252

Exclusion Criteria

1. Treatment with inhibitors of aldosterone mediated effects (e.g.,
mineralocorticoid receptor antagonists such as spironolactone), or
intake of other potassium sparing
diuretics (e.g., amiloride) within 7 days prior to first randomisation or
planned during trial treatment phase.
2. Treatment with other Renin Angiotensin Aldosterone System (RAAS)
interventions (apart from either ACEi or ARB) within 4 weeks prior to
Visit 1 and throughout screening or planned during the trial.
3. Type 1 diabetes mellitus, or history of other autoimmune causes of
diabetes mellitus (e.g. LADA)
4. Patients at increased risk of ketoacidosis in the opinion of the
investigator.
5. Currently receiving SGLT-2 or SGLT-1/2 inhibitor or planned initiation
during the trial.
Further criteria apply.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The trial will compare 3 doses of BI 690517 with placebo in patients with<br>diabetic and nondiabetic CKD randomised to empagliflozin or placebo as background therapy<br>(established during the randomised run-in).;Secondary Objective: Secondary objectives will be as above but in subpopulations of (1)<br>placebo background therapy (2) empagliflozin background therapy.;Primary end point(s): 1) Change from treatment period baseline in log transformed Urine Albumin<br>Creatinine Ratio (UACR) measured in First Morning Void urine after 14 weeks.;Timepoint(s) of evaluation of this end point: 1) 14 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): 1) UACR response I, defined as decrease of at least 30% absolute<br>change in First Morning Void urine of UACR from treatment period<br>baseline to 14 weeks.<br>2) UACR response II, defined as decrease of at least 15% absolute<br>change in First Morning Void urine of UACR from treatment period<br>baseline to 14 weeks.;Timepoint(s) of evaluation of this end point: 1) 14 weeks<br>2) 14 weeks

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