A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic 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 Non-diabetic Kidney Disease

This study is open to adults who have kidney disease that is not caused by diabetes. The purpose of the study is to find out whether a medicine called avenciguat (BI 685509) improves kidney function. Three different doses of avenciguat are tested in this study.

Participants get either one of the three doses of avenciguat or placebo. It is decided by chance who gets which avenciguat dose and who gets placebo. Participants take avenciguat or placebo as tablets 3 times a day. Placebo tablets look like avenciguat tablets but do not contain any medicine. Participants continue taking their usual medicine for 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 avenciguat and placebo. During the study, the doctors also regularly check the general health of the participants.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Drug: Placebo; Drug: Avenciguat

• Study Type: Interventional
• Enrollment (Actual): 261
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1023AAB
    • STAT Research
  • Caba, Argentina, C1060ABN
    • CEDIC - Centro de Investigacion Clinica
  • Caba, Argentina, C1431FWO
    • CEMIC
  • Cordoba, Argentina, X5000AAW
    • Instituto Privado de Investigaciones Clínica Córdoba S.A.
  • Mar del Plata, Argentina, B7600FZN
    • Instituto de Investigaciones Clinicas Mar del Plata
  • Mar del Plata, Argentina, B7600FYK
    • Centro de Investigaciones Médicas Mar del Plata
  • Rosario, Argentina, S2000AJU
    • Instituto Médico Catamarca - IMEC
  • Santa Fe, Argentina, S3000FSP
    • CEDIR Santa Fe
  • 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
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital
• Canada
  • Alberta
    • Red Deer, Alberta, Canada, T4P 1K4
      • CARe Clinic
  • Ontario
    • Stouffville, Ontario, Canada, L4A 1H2
      • Stouffville Medical Centre
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital
    • Toronto, Ontario, Canada, M9V 4B4
      • Albion Finch Medical Centre
    • Waterloo, Ontario, Canada, N2J 1C4
      • Fadia El Boreky Medicine Professional
• China
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Beijing, China, 100191
    • Peking University Third Hospital
  • Beijing, China, 100034
    • Peking University First Hospital
  • Chengdu, China, 610072
    • People's Hospital of Sichuan Province
  • Chongqing, China, 400016
    • Second Affiliated Hospital Chongqing Medical University
  • Xuancheng, China, 242000
    • The People's Hospital Of Xuancheng City
• Denmark
  • Aarhus N, Denmark, 8200
    • Aarhus University Hospital
  • Herlev, Denmark, 2730
    • Herlev and Gentofte Hospital
  • Holbæk, Denmark, 4300
    • Holbæk Sygehus
  • Roskilde, Denmark, 4000
    • Sjællands Universitetshospital
• Germany
  • Hannover, Germany, 30459
    • Klinikum Region Hannover GmbH
  • Lübeck, Germany, 23538
    • Universitätsklinikum Schleswig-Holstein, Campus Lübeck
• 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
  • Hong Kong, Hong Kong, 999077
    • Princess Margaret Hospital
• Japan
  • Aichi, Nagoya, Japan, 455-8530
    • Chubu Rosai Hospital
  • Aichi, Nagoya, Japan, 457-8511
    • Daido Hospital
  • Chiba, Urayasu, Japan, 279-0021
    • Juntendo University Urayasu 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
  • Kyoto, Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Mie, Kuwana, Japan, 511-0061
    • Kuana City Medical Center
  • Nagano, Matsumoto, Japan, 390-8621
    • Shinshu University Hospital
  • Okayama, Kurashiki, Japan, 701-0192
    • Kawasaki Medical School Hospital
  • Saitama, Iruma-gun, Japan, 350-0495
    • Saitama Medical University Hospital
  • Shizuoka, Yaizu, Japan, 425-8505
    • Yaizu City Hospital
  • Tokyo, Bunkyo-ku, Japan, 113-8655
    • The University of Tokyo Hospital
  • Tokyo, Chuo-ku, Japan, 103-0027
    • Tokyo-Eki Center-building Clinic
  • Tokyo, Itabashi-ku, Japan, 173-8610
    • Nihon University Itabashi Hospital
• Malaysia
  • Cheras, Kuala Lumpur, Malaysia, 56000
    • University Kebangsaan Malaysia
  • Ipoh, Perak, Malaysia, 30450
    • Hospital Raja Permaisuri Bainun
  • Kelantan, Malaysia, 16150
    • Universiti Sains Malaysia Hospital
  • Kuala Lumpur, Malaysia, 59100
    • University of Malaya Medical Centre
  • Selangor, Malaysia, 68100
    • Hospital Selayang
• Mexico
  • Aguascalientes, Mexico, 20259
    • Centenario Hospital Miguel Hidalgo
  • Aguascalientes, Mexico, 20230
    • Centro de Investigacion Cardiometabolica de Aguascalientes
  • Ciudad de Mexico, Mexico, 14080
    • Instituto Nacional de Cardiologia Ignacio Chavez
  • Ciudad de México, Mexico, 14000
    • Instituto Nacional de Cs Médicas y Nutrición S Zubiran
  • Monterrey, Mexico, 64460
    • Hospital Universitario Dr Jose Eleuterio Gonzalez
  • México, Mexico, 06700
    • Clinstile S.A. de C.V.
• New Zealand
  • Dunedin, New Zealand, 9054
    • Dunedin Hospital
  • Paraparaumu, New Zealand, 5032
    • P3 Research Kapiti
  • Tauranga, New Zealand, 3110
    • P3 Research
• Poland
  • Chrzanow, Poland, 32-500
    • Cardiovascular Centre of Malopolska
  • Krakow, Poland, 30-510
    • Pratia MCM Krakow
  • Lodz, Poland, 92-213
    • Cent.Clin.Hosp.Med.Univ.Lodz
  • Oswiecim, Poland, 32600
    • Medicome Limited Liability Company
• Portugal
  • Aveiro, Portugal, 3810-164
    • ULS da Região de Aveiro
  • Carnaxide, Portugal, 2790-134
    • CHLO, EPE - Hospital de Santa Cruz
  • Lisboa, Portugal, 1649-035
    • ULS de Santa Maria, E.P.E
  • Porto, Portugal, 4200-319
    • Centro Hospitalar Universitário São João,EPE
• Russian Federation
  • Moscow, Russian Federation, 119992
    • Moscow 1st State Med.Univ.n.a.I.M.Sechenov
  • St. Petersburg, Russian Federation, 197110
    • St. Petersburg GUZ City Hospital no. 31, St. Petersburg
• Spain
  • Barcelona, Spain, 08035
    • Hospital Vall d'Hebron
  • L'Hospitalet de Llobregat, Spain, 08907
    • Hospital de Bellvitge
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Pamplona, Spain, 31008
    • Clinica Universidad de Navarra
  • Sevilla, Spain, 41009
    • Hospital Virgen Macarena
  • Valencia, Spain, 46010
    • Hospital Clínico de Valencia
  • Valencia, Spain, 46017
    • Hospital Dr. Peset
• Sweden
  • Stockholm, Sweden, 11329
    • ProbarE i Stockholm
• United Kingdom
  • Corby, United Kingdom, NN17 2UR
    • Lakeside Surgery
  • 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
    • Canyon Country, California, United States, 91351
      • Clearview Medical Research, LLC
    • Rancho Cucamonga, California, United States, 91730
      • Rancho Cucamonga Clinical Trials
    • Victorville, California, United States, 92395
      • Kidney & Hypertension Center
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Chase Medical Research, LLC
  • Delaware
    • Newark, Delaware, United States, 19713
      • Nephrology Associates, P.A.
  • Florida
    • Hialeah, Florida, United States, 33012
      • Indago Research and Health Center
    • Miami, Florida, United States, 33032
      • Homestead Associates In Research
    • Miami, Florida, United States, 33155
      • Bioclinical Research Alliance, Inc.
    • Miami, Florida, United States, 33165
      • Alma Clinical Research, Inc.
    • 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
  • Idaho
    • Boise, Idaho, United States, 83706
      • Boise Kidney and Hypertension, PLLC
  • Illinois
    • Chicago, Illinois, United States, 60643
      • Research by Design, LLC
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70808
      • Renal Associates of Baton Rouge
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Davita Clinical Research
    • Las Vegas, Nevada, United States, 89128
      • Nevada Kidney Disease and Hypertension Centers, PLLC
  • New Jersey
    • Jersey City, New Jersey, United States, 07305
      • New Jersey Kidney Care, LLC
  • 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
    • El Paso, Texas, United States, 79925
      • Davita Clinical Research
    • San Antonio, Texas, United States, 78212
      • Clinical Advancement Center, PLLC
    • Shenandoah, Texas, United States, 77384
      • Kidney Specialists of North Houston, PLLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Signed and dated written informed consent in accordance with International Council on Harmonisation-Good Clinical Practice (ICH-GCP) and local legislation prior to admission to the trial.
• Male or female patients aged ≥18 years at time of consent.
• Estimated glomerular filtration rate (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.
• Urine albumin creatinine ratio (UACR) ≥ 200 and < 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.
• Patients with macroalbuminuria (>300 mg/g) should be treated with the highest tolerated dose of either Angiotensin Converting Enzyme inhibitor (ACEi) or Angiotensin Receptor Blocker (ARB) (but not both). For patients with microalbuminuria the use of ACEi or ARB is at the discretion of the Investigator. Treatment should be at a stable dose for ≥ 4 weeks before Visit 1 with no planned change of the therapy during the trial.
• 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 drugs (NSAIDs), endothelin receptor antagonists, systemic steroids or Sodium-glucose co-transporter-2 (SGLT2) inhibitors.
• In the Investigator's judgment any kind of diagnosed chronic kidney disease whose primary cause is clinically not considered to be of diabetic origin.

Further inclusion criteria apply

Exclusion Criteria:

• 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), Nitric Oxide (NO) donors including nitrates, soluble Guanylate Cyclase (sGC)-stimulators/activators (other than trial treatment) or any other restricted medication (including Organic Anion-Transporting Polypeptide 1B1 and 1B3 (OATP1B1/3) inhibitors, Uridine 5'-diphosphate -glucuronosyltransferase (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.
• Any clinically relevant laboratory value from screening until start of trial treatment which, in the investigator's judgement, puts the patient at additional risk.
• Diagnosed with diabetic kidney disease.
• Any immunosuppression therapy or immunotherapy in last 3 months prior to visit 1 and throughout screening and baseline run-in (except prednisolone ≤10 mg or equivalent).
• 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.
• Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment.
• Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment.
• 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

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Dose group 1: Matching placebo; Matching placebo for low dose.	Drug: Placebo; Placebo
Placebo Comparator: Dose group 2: Matching placebo; Matching placebo for low dose followed by up-titration to medium dose.	Drug: Placebo; Placebo
Placebo Comparator: Dose group 3: Matching placebo; Matching placebo for low dose followed by up-titration to medium dose, followed by up-titration to high dose.	Drug: Placebo; Placebo
Experimental: Dose group 1: Avenciguat; Low dose.	Drug: Avenciguat; Avenciguat; Other Names: BI 685509
Experimental: Dose group 2: Avenciguat; Low dose followed by up-titration to medium dose.	Drug: Avenciguat; Avenciguat; Other Names: BI 685509
Experimental: Dose group 3: Avenciguat; Low dose followed by up-titration to medium dose, followed by up-titration to high-dose.	Drug: Avenciguat; Avenciguat; Other Names: BI 685509

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment.	Up to 20 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment.	Up to 20 weeks
Proportion of patients achieving UACR decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment.	Up to 20 weeks
Proportion of patients achieving UACR decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment.	Up to 20 weeks

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): August 15, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: February 1, 2021
• First Submitted That Met QC Criteria: February 1, 2021
• First Posted (Actual): February 3, 2021

Study Record Updates

• Last Update Posted (Estimated): May 7, 2024
• Last Update Submitted That Met QC Criteria: May 6, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Disease Attributes; Renal Insufficiency; Chronic Disease; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: 1366-0022; 2020-002930-33 (EudraCT Number)

Plan for Individual participant data (IPD)

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

IPD Plan Description

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this 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". Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to 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.

The data shared are the raw clinical study data sets.

• IPD Sharing Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
• 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 both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing 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