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

NCT ID: NCT04736628

Last Updated: 2024-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 261 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2023-09-21

Brief Summary

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.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Avenciguat 1 mg TID

TID=ter in die (3 times a day)

Group Type: EXPERIMENTAL

Avenciguat

Intervention Type: DRUG

Avenciguat

Avenciguat 2 mg TID

Group Type: EXPERIMENTAL

Avenciguat

Intervention Type: DRUG

Avenciguat

Avenciguat 3 mg TID

Group Type: EXPERIMENTAL

Avenciguat

Intervention Type: DRUG

Avenciguat

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Avenciguat

Avenciguat

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

Other Intervention Names

BI 685509

Eligibility Criteria

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.

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Boehringer Ingelheim

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Queen Mary Hospital

Hong Kong, , Hong Kong

Tung Wah Hospital

Hong Kong, , Hong Kong

Chubu Rosai Hospital

Aichi, Nagoya, , Japan

Daido Hospital

Aichi, Nagoya, , Japan

Juntendo University Urayasu Hospital

Chiba, Urayasu, , Japan

Kurume University Hospital

Fukuoka, Kurume, , Japan

Nakayamadera Imai Clinic

Hyogo, Takarazuka, , Japan

Takai Naika Clinic

Kanagawa, Kamakura, , Japan

Kyoto University Hospital

Kyoto, Kyoto, , Japan

Kuana City Medical Center

Mie, Kuwana, , Japan

Shinshu University Hospital

Nagano, Matsumoto, , Japan

Kawasaki Medical School Hospital

Okayama, Kurashiki, , Japan

Saitama Medical University Hospital

Saitama, Iruma-gun, , Japan

Yaizu City Hospital

Shizuoka, Yaizu, , Japan

The University of Tokyo Hospital

Tokyo, Bunkyo-ku, , Japan

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, , Japan

Nihon University Itabashi Hospital

Tokyo, Itabashi-ku, , Japan

University Kebangsaan Malaysia

Cheras, Kuala Lumpur, , Malaysia

Hospital Raja Permaisuri Bainun

Ipoh, Perak, , Malaysia

Universiti Sains Malaysia Hospital

Kelantan, , Malaysia

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Selayang

Kuala Selangor, , Malaysia

Centro de Investigacion Cardiometabolica de Aguascalientes

Aguascalientes, , Mexico

Centenario Hospital Miguel Hidalgo

Aguascalientes, , Mexico

Instituto Nacional de Cs Médicas y Nutrición S Zubiran

Mexico City, , Mexico

Instituto Nacional de Cardiologia Ignacio Chavez

Mexico City, , Mexico

Clinstile S.A. de C.V.

México, , Mexico

Hospital Universitario Dr Jose Eleuterio Gonzalez

Monterrey, , Mexico

Dunedin Hospital

Dunedin, , New Zealand

P3 Research Kapiti

Paraparaumu, , New Zealand

P3 Research

Tauranga, , New Zealand

Cardiovascular Centre of Malopolska

Chrzanów, , Poland

Pratia MCM Krakow

Krakow, , Poland

Cent.Clin.Hosp.Med.Univ.Lodz

Lodz, , Poland

Medicome Limited Liability Company

Oświęcim, , Poland

ULS da Região de Aveiro

Aveiro, , Portugal

CHLO, EPE - Hospital de Santa Cruz

Carnaxide, , Portugal

ULS de Santa Maria, E.P.E

Lisbon, , Portugal

Centro Hospitalar Universitário São João,EPE

Porto, , Portugal

Moscow 1st State Med.Univ.n.a.I.M.Sechenov

Moscow, , Russia

St. Petersburg GUZ City Hospital no. 31, St. Petersburg

Saint Petersburg, , Russia

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital de Bellvitge

L'Hospitalet de Llobregat, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Clínica Universidad de Navarra

Pamplona, , Spain

Hospital Virgen Macarena

Seville, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

Hospital Dr. Peset

Valencia, , Spain

ProbarE i Stockholm

Stockholm, , Sweden

Lakeside Surgery

Corby, , United Kingdom

University Hospital Coventry

Coventry, , United Kingdom

Barts and The London School of Medicine and Dentistry

London, , United Kingdom

Clearview Medical Research, LLC

Canyon Country, California, United States

Rancho Cucamonga Clinical Trials

Rancho Cucamonga, California, United States

Kidney & Hypertension Center

Victorville, California, United States

Chase Medical Research, LLC

Waterbury, Connecticut, United States

Nephrology Associates, P.A.

Newark, Delaware, United States

Indago Research and Health Center

Hialeah, Florida, United States

Homestead Associates in Research

Miami, Florida, United States

Bioclinical Research Alliance, Inc.

Miami, Florida, United States

Alma Clinical Research, Inc.

Miami, Florida, United States

Panax Clinical Research

Miami Lakes, Florida, United States

Davita Clinical Research

Columbus, Georgia, United States

Meridian Clinical Research, LLC

Savannah, Georgia, United States

Boise Kidney and Hypertension, PLLC

Boise, Idaho, United States

Research by Design, LLC

Chicago, Illinois, United States

Renal Associates of Baton Rouge

Baton Rouge, Louisiana, United States

DaVita Clinical Research

Las Vegas, Nevada, United States

Nevada Kidney Disease and Hypertension Centers, PLLC

Las Vegas, Nevada, United States

New Jersey Kidney Care, LLC

Jersey City, New Jersey, United States

Brookview Hills Research Associates LLC

Winston-Salem, North Carolina, United States

Knoxville Kidney Center PLLC

Knoxville, Tennessee, United States

Davita Clinical Research

El Paso, Texas, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

Kidney Specialists of North Houston, PLLC

Shenandoah, Texas, United States

STAT Research

CABA, , Argentina

CEDIC - Centro de Investigacion Clinica

CABA, , Argentina

CEMIC

CABA, , Argentina

Instituto Privado de Investigaciones Clínica Córdoba S.A.

Córdoba, , Argentina

Centro de Investigaciones Médicas Mar del Plata

Mar del Plata, , Argentina

Instituto de Investigaciones Clinicas Mar del Plata

Mar del Plata, , Argentina

Instituto Médico Catamarca - IMEC

Rosario, , Argentina

CEDIR Santa Fe

Santa Fe, , Argentina

CEREHA S.A.- Centro de Estudios Renales e Hipertensión Arterial

Sarandí, , Argentina

Renal Research, Gosford

Gosford, New South Wales, Australia

Nepean Hospital

Kingswood, New South Wales, Australia

Macquarie University

Macquarie Park, New South Wales, Australia

Royal North Shore Hospital

St Leonards, New South Wales, Australia

Westmead Hospital

Westmead, New South Wales, Australia

Austin Health

Heidelberg, Victoria, Australia

Royal Melbourne Hospital

Parkville, Victoria, Australia

CARe Clinic

Red Deer, Alberta, Canada

Stouffville Medical Centre

Stouffville, Ontario, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Albion Finch Medical Centre

Toronto, Ontario, Canada

Fadia El Boreky Medicine Professional

Waterloo, Ontario, Canada

Peking University First Hospital

Beijing, , China

Peking University People's Hospital

Beijing, , China

Peking University Third Hospital

Beijing, , China

People's Hospital of Sichuan Province

Chengdu, , China

Second Affiliated Hospital Chongqing Medical University

Chongqing, , China

The People's Hospital Of Xuancheng City

Xuancheng, , China

Aarhus University Hospital

Aarhus N, , Denmark

Herlev and Gentofte Hospital

Herlev, , Denmark

Holbæk Sygehus

Holbæk, , Denmark

Sjællands Universitetshospital

Roskilde, , Denmark

Klinikum Region Hannover GmbH

Hanover, , Germany

Universitätsklinikum Schleswig-Holstein, Campus Lübeck

Lübeck, , Germany

Prince of Wales Hospital

Hong Kong, , Hong Kong

Princess Margaret Hospital

Hong Kong, , Hong Kong

Countries

United States; Argentina; Australia; Canada; China; Denmark; Germany; Hong Kong; Japan; Malaysia; Mexico; New Zealand; Poland; Portugal; Russia; Spain; Sweden; United Kingdom

References

Heerspink HJL, Cherney D, Gafor AHA, Gorriz JL, Pergola PE, Tang SCW, Desch M, Iliev H, Sun Z, Steubl D, Nangaku M. Effect of Avenciguat on Albuminuria in Patients with CKD: Two Randomized Placebo-Controlled Trials. J Am Soc Nephrol. 2024 Sep 1;35(9):1227-1239. doi: 10.1681/ASN.0000000000000418. Epub 2024 May 25.

Reference Type: DERIVED

PMID: 38795055 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.mystudywindow.com

Related Info

Other Identifiers

2020-002930-33

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1366-0022

Identifier Type: -

Identifier Source: org_study_id