A Study to Test the Effect of Different Doses of BI 685509 on Kidney Function in People With Diabetic Kidney Disease

Randomised, Double-blind (Within Dose Groups), Placebo-controlled and Parallel Group Trial to Investigate the Effects of Different Doses of Oral BI 685509 Given Over 20 Weeks on UACR Reduction in Patients With Diabetic Kidney Disease

This study is open to adults with diabetic kidney disease. The purpose of the study is to find out whether a medicine called BI 685509 improves kidney function. Three different doses of BI 685509 are tested in this study.

Participants get either one of the three doses of BI 685509 or placebo. It is decided by chance who gets which BI 685509 dose and who gets placebo. Participants take BI 685509 or placebo as tablets 3 times a day. Placebo tablets look like BI 685509 tablets but do not contain any medicine. Participants continue taking their usual medicine for diabetes and kidney disease throughout the study.

Participants are in the study for about 7 months. During this time, they visit the study site about 11 times. Where possible, about 6 of the 11 visits can be done at the participant's home instead of the study site. The trial staff may also contact the participants by phone or video call.

Kidney function is assessed based on the analysis of urine samples, which participants collect at home. At the end of the trial the results are compared between the different doses of BI 685509 and placebo. During the study, the doctors also regularly check the general health of the participants.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathies
• Intervention / Treatment: Drug: BI 685509; Drug: Placebo matching BI 685509

• Study Type: Interventional
• Enrollment (Actual): 243
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1060ABN
    • CEDIC - Centro de Investigacion Clinica
  • Capital Federal, Argentina, C1405BCH
    • Instituto Médico Especializado
  • Cordoba, Argentina, X5000AAW
    • Instituto Privado de Investigaciones Clinica Cordoba S.A.
  • Mar del Plata, Argentina, B7600FYK
    • Centro de Investigaciones Medicas Mar Del Plata
  • Rosario, Argentina, S2000AJU
    • Instituto Medico Catamarca - IMEC
  • Sarandi, Argentina, B1872EEB
    • CEREHA S.A.- Centro de Estudios Renales e Hipertensión Arterial
• Australia
  • New South Wales
    • Gosford, New South Wales, Australia, 2250
      • Renal Research, Gosford
    • Kingswood, New South Wales, Australia, 2747
      • Nepean Hospital
    • Macquarie Park, New South Wales, Australia, 2109
      • Macquarie University
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Austin Health
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4P 1K4
      • CARe Clinic
  • Ontario
    • Toronto, Ontario, Canada, M9V 4B4
      • Albion Finch Medical Centre
    • Waterloo, Ontario, Canada, N2J 1C4
      • Fadia El Boreky Medicine Professional
• China
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Chongqing, China, 400016
    • Second Affiliated Hospital Chongqing Medical University
  • Sichuan, China, 610031
    • People's Hospital of Sichuan Province
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Herlev, Denmark, 2730
    • Steno Diabetes Center Copenhagen
  • Roskilde, Denmark, 4000
    • Sjællands Universitetshospital
• Hong Kong
  • Hong Kong, Hong Kong, 999077
    • Prince of Wales Hospital
  • Hong Kong, Hong Kong
    • Tung Wah Hospital
  • Hong Kong, Hong Kong, 999077
    • Queen Mary Hospital
• Japan
  • Aichi, Nagoya, Japan, 455-8530
    • Chubu Rosai Hospital
  • Aichi, Nagoya, Japan, 457-8511
    • Daido Hospital
  • Fukuoka, Kurume, Japan, 830-0011
    • Kurume University Hospital
  • Hyogo, Takarazuka, Japan, 665-0861
    • Nakayamadera Imai Clinic
  • Kanagawa, Kamakura, Japan, 247-0056
    • Takai Naika Clinic
  • Okayama, Kurashiki, Japan, 701-0192
    • Kawasaki Medical School Hospital
  • Osaka, Osaka, Japan, 558-8558
    • Osaka General Medical Center
  • Osaka, Suita, Japan, 565-0853
    • OCROM Clinic
  • Saitama, Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8655
    • The University of Tokyo Hospital
  • Tokyo, Chuo-ku, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic
  • Tokyo, Shinjyuku-ku, Japan, 160-0008
    • ToCROM Clinic
• Malaysia
  • Cheras, Kuala Lumpur, Malaysia, 56000
    • University Kebangsaan Malaysia
  • Kelantan, Malaysia, 16150
    • universiti Sains Malaysia hospital
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
  • Selangor, Malaysia, 68100
    • Hospital Selayang
• Mexico
  • Aguascalientes, Mexico, 20230
    • Hospital Cardiologica Aguascalientes
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
  • México, Mexico, 06700
    • Clinstile S.A. de C.V.
• Netherlands
  • Dordrecht, Netherlands, 3318 AT
    • Albert SchweitzerZiekenhuis
  • GA Utrecht, Netherlands, 3508
    • Universitair Medisch Centrum Utrecht
• New Zealand
  • Paraparaumu, New Zealand, 5032
    • P3 Research Kapiti
  • Tauranga, New Zealand, 3110
    • P3 Research
• Poland
  • Bialystok, Poland, 15-375
    • SPECDERM Poznanska General Partnership
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Oswiecim, Poland, 32-600
    • Medicome Limited Liability Company
  • Warsaw, Poland, 00710
    • NBR Polska
• Portugal
  • Aveiro, Portugal, 3810-164
    • ULS da Região de Aveiro
  • Lisboa, Portugal, 1250-189
    • APDP - Associação Protectora dos Diabéticos de Portugal
• Spain
  • A Coruña, Spain, 15006
    • Hospital A Coruña
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
• United Kingdom
  • Coventry, United Kingdom, CV2 2DX
    • University Hospital Coventry
  • London, United Kingdom, EC1M 6BQ
    • Barts and The London School of Medicine and Dentistry
• United States
  • California
    • Victorville, California, United States, 92395
      • Kidney & Hypertension Center
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Miami Lakes, Florida, United States, 33014
      • Panax Clinical Research
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Davita Clinical Research
    • Savannah, Georgia, United States, 31406
      • Meridian Clinical Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Davita Clinical Research
  • New York
    • Bronx, New York, United States, 10461
      • Total Renal Research
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27103
      • Brookview Hills Research Associates LLC
  • Tennessee
    • Knoxville, Tennessee, United States, 37923
      • Knoxville Kidney Center PLLC
  • Texas
    • Houston, Texas, United States, 77054
      • Davita Clinical Research
    • Lufkin, Texas, United States, 75904
      • Texas Institute for Kidney and Endocrine Disorders
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC
    • San Antonio, Texas, United States, 78240
      • Davita Clinical Research
    • Shenandoah, Texas, United States, 77384
      • Kidney Specialists of North Houston, PLLC
  • Virginia
    • Norfolk, Virginia, United States, 23510
      • Tidewater Kidney Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. Signed and dated written informed consent in accordance with International Council of Harmonisation-Good Clinical Practice (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. Urine Albumin Creatinine Ratio (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 Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (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, Non-steroidal anti-inflammatory drug(s) (NSAIDs), endothelin receptor antagonists, systemic steroids or Sodium-Glucose co-Transporter-2 (SGLT2) inhibitors.
7. Patients with stable type 1 or type 2 diabetes mellitus, diagnosed before informed consent. Treatment (including SGLT2 inhibitor and/or Glucagon-Like Peptide 1 (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.

Further inclusion criteria apply.

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 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 Chronic Kidney Disease (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) 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 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) (or is known to have a positive test) from screening until randomisation.

Further exclusion criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo matching BI 685509; film-coated tablet
Experimental: BI 685509 1 mg TID	Drug: BI 685509; film-coated tablet; Other Names: Avenciguat
Experimental: BI 685509 2 mg TID; Low dose followed by up-titration to medium dose.	Drug: BI 685509; film-coated tablet; Other Names: Avenciguat
Experimental: BI 685509 3 mg TID; Low dose followed by up-titration to medium dose, followed by up-titration to high-dose.	Drug: BI 685509; film-coated tablet; Other Names: Avenciguat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment	Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) after 20 weeks is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12 and Week 20) as well as random effects of patient. The Least Squares Mean (Standard error) at Week 20 is reported.	The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2 and Week -1) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in First Morning Void Urine After 20 Weeks of Trial Treatment	Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in First Morning Void urine after 20 weeks of trial treatment is reported. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12 and Week 20) as well as random effects of patient. The Least Squares Mean (Standard error) at Week 20 is reported.	The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2 and Week -1) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.
Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment	Number of patients achieving Urine Albumin Creatinine Ratio (UACR) decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample.	Baseline (day -14 and -7) and week 20 (day 141).
Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment	Number of patients achieving Albumin Creatinine Ratio (UACR) decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment. is reported. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day.	Baseline (day -14 and -7) and week 20 (day 141).

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): December 27, 2022

Study Registration Dates

• First Submitted: February 9, 2021
• First Submitted That Met QC Criteria: February 9, 2021
• First Posted (Actual): February 11, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies
• Other Study ID Numbers: 1366-0005; 2020-002929-28 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Once the criteria in section "Time Frame" are fulfilled, researchers can use the following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Furthermore, researchers can request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

• IPD Sharing Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• IPD Sharing Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No