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

NCT ID: NCT04750577

Last Updated: 2024-07-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2022-12-27

Brief Summary

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.

Conditions

Diabetic Nephropathies

Study Design

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

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo matching BI 685509

Intervention Type: DRUG

film-coated tablet

BI 685509 1 mg TID

Group Type: EXPERIMENTAL

BI 685509

Intervention Type: DRUG

film-coated tablet

BI 685509 2 mg TID

Low dose followed by up-titration to medium dose.

Group Type: EXPERIMENTAL

BI 685509

Intervention Type: DRUG

film-coated tablet

BI 685509 3 mg TID

Low dose followed by up-titration to medium dose, followed by up-titration to high-dose.

Group Type: EXPERIMENTAL

BI 685509

Intervention Type: DRUG

film-coated tablet

Interventions

Placebo matching BI 685509

film-coated tablet

Intervention Type: DRUG

BI 685509

film-coated tablet

Intervention Type: DRUG

Other Intervention Names

Avenciguat

Eligibility Criteria

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.

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.

• 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

Kidney & Hypertension Center

Victorville, California, United States

Chase Medical Research, LLC

Waterbury, Connecticut, United States

Indago Research and Health Center

Hialeah, 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

Research by Design, LLC

Chicago, Illinois, United States

DaVita Clinical Research

Las Vegas, Nevada, United States

Total Renal Research

The Bronx, New York, United States

Brookview Hills Research Associates LLC

Winston-Salem, North Carolina, United States

Knoxville Kidney Center PLLC

Knoxville, Tennessee, United States

DaVita Clinical Research

Houston, Texas, United States

Texas Institute for Kidney and Endocrine Disorders

Lufkin, Texas, United States

Clinical Advancement Center, PLLC

San Antonio, Texas, United States

DaVita Clinical Research

San Antonio, Texas, United States

Kidney Specialists of North Houston, PLLC

Shenandoah, Texas, United States

Tidewater Kidney Specialists

Norfolk, Virginia, United States

CEDIC - Centro de Investigacion Clinica

CABA, , Argentina

Instituto Médico Especializado

Capital Federal, , Argentina

Instituto Privado de Investigaciones Clínica Córdoba S.A.

Córdoba, , Argentina

Centro de Investigaciones Médicas Mar del Plata

Mar del Plata, , Argentina

Instituto Médico Catamarca - IMEC

Rosario, , 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

CARe Clinic

Red Deer, Alberta, Canada

Albion Finch Medical Centre

Toronto, Ontario, Canada

Fadia El Boreky Medicine Professional

Waterloo, Ontario, Canada

Peking University First Hospital

Beijing, , China

Peking University Third Hospital

Beijing, , China

Second Affiliated Hospital Chongqing Medical University

Chongqing, , China

People's Hospital of Sichuan Province

Sichuan, , China

Aarhus University Hospital

Aarhus N, , Denmark

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Sjællands Universitetshospital

Roskilde, , Denmark

Prince of Wales Hospital

Hong Kong, , Hong Kong

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

Kurume University Hospital

Fukuoka, Kurume, , Japan

Nakayamadera Imai Clinic

Hyogo, Takarazuka, , Japan

Takai Naika Clinic

Kanagawa, Kamakura, , Japan

Kawasaki Medical School Hospital

Okayama, Kurashiki, , Japan

Osaka General Medical Center

Osaka, Osaka, , Japan

OCROM Clinic

Osaka, Suita, , Japan

Saitama Medical University Hospital

Saitama, Iruma-gun, , Japan

The University of Tokyo Hospital

Tokyo, Bunkyo-ku, , Japan

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, , Japan

ToCROM Clinic

Tokyo, Shinjyuku-ku, , Japan

University Kebangsaan Malaysia

Cheras, Kuala Lumpur, , Malaysia

Universiti Sains Malaysia Hospital

Kelantan, , Malaysia

University of Malaya Medical Centre

Kuala Lumpur, , Malaysia

Hospital Selayang

Kuala Selangor, , Malaysia

Hospital Cardiologica Aguascalientes

Aguascalientes, , Mexico

Centenario Hospital Miguel Hidalgo

Aguascalientes, , Mexico

Clinstile S.A. de C.V.

México, , Mexico

Hospital Universitario Dr Jose Eleuterio Gonzalez

Monterrey, , Mexico

Albert SchweitzerZiekenhuis

Dordrecht, , Netherlands

Universitair Medisch Centrum Utrecht

GA Utrecht, , Netherlands

P3 Research Kapiti

Paraparaumu, , New Zealand

P3 Research

Tauranga, , New Zealand

SPECDERM Poznanska General Partnership

Bialystok, , Poland

Pratia MCM Krakow

Krakow, , Poland

Medicome Limited Liability Company

Oświęcim, , Poland

NBR Polska

Warsaw, , Poland

ULS da Região de Aveiro

Aveiro, , Portugal

APDP - Associação Protectora dos Diabéticos de Portugal

Lisbon, , Portugal

Hospital A Coruña

A Coruña, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Virgen Macarena

Seville, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

University Hospital Coventry

Coventry, , United Kingdom

Barts and The London School of Medicine and Dentistry

London, , United Kingdom

Countries

United States; Argentina; Australia; Canada; China; Denmark; Hong Kong; Japan; Malaysia; Mexico; Netherlands; New Zealand; Poland; Portugal; Spain; 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

2020-002929-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1366-0005

Identifier Type: -

Identifier Source: org_study_id