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

Chronic Kidney Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04736628
• Other study ID #: 1366-0022
• Secondary ID: 2020-002930-33
• Status: Completed
• Phase: Phase 2
• Start date: April 27, 2021
• Est. completion date: September 21, 2023

Study information

• Verified date: May 2024
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 261
• Est. completion date: September 21, 2023
• Est. primary completion date: August 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Drug:
• Avenciguat
Avenciguat
• Placebo
Placebo

Locations

Country	Name	City	State
Argentina	CEDIC - Centro de Investigacion Clinica	Caba
Argentina	CEMIC	Caba
Argentina	STAT Research	Caba
Argentina	Instituto Privado de Investigaciones Clínica Córdoba S.A.	Cordoba
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	Sarandi
Australia	Renal Research, Gosford	Gosford	New South Wales
Australia	Austin Health	Heidelberg	Victoria
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	Macquarie University	Macquarie Park	New South Wales
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Canada	CARe Clinic	Red Deer	Alberta
Canada	Stouffville Medical Centre	Stouffville	Ontario
Canada	Albion Finch Medical Centre	Toronto	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Fadia El Boreky Medicine Professional	Waterloo	Ontario
China	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
Denmark	Aarhus University Hospital	Aarhus N
Denmark	Herlev and Gentofte Hospital	Herlev
Denmark	Holbæk Sygehus	Holbæk
Denmark	Sjællands Universitetshospital	Roskilde
Germany	Klinikum Region Hannover GmbH	Hannover
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck
Hong Kong	Prince of Wales Hospital	Hong Kong
Hong Kong	Princess Margaret Hospital	Hong Kong
Hong Kong	Queen Mary Hospital	Hong Kong
Hong Kong	Tung Wah Hospital	Hong Kong
Japan	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
Malaysia	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	Selangor
Mexico	Centenario Hospital Miguel Hidalgo	Aguascalientes
Mexico	Centro de Investigacion Cardiometabolica de Aguascalientes	Aguascalientes
Mexico	Instituto Nacional de Cardiologia Ignacio Chavez	Ciudad de Mexico
Mexico	Instituto Nacional de Cs Médicas y Nutrición S Zubiran	Ciudad de México
Mexico	Clinstile S.A. de C.V.	México
Mexico	Hospital Universitario Dr Jose Eleuterio Gonzalez	Monterrey
New Zealand	Dunedin Hospital	Dunedin
New Zealand	P3 Research Kapiti	Paraparaumu
New Zealand	P3 Research	Tauranga
Poland	Cardiovascular Centre of Malopolska	Chrzanow
Poland	Pratia MCM Krakow	Krakow
Poland	Cent.Clin.Hosp.Med.Univ.Lodz	Lodz
Poland	Medicome Limited Liability Company	Oswiecim
Portugal	ULS da Região de Aveiro	Aveiro
Portugal	CHLO, EPE - Hospital de Santa Cruz	Carnaxide
Portugal	ULS de Santa Maria, E.P.E	Lisboa
Portugal	Centro Hospitalar Universitário São João,EPE	Porto
Russian Federation	Moscow 1st State Med.Univ.n.a.I.M.Sechenov	Moscow
Russian Federation	St. Petersburg GUZ City Hospital no. 31, St. Petersburg	St. Petersburg
Spain	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	Sevilla
Spain	Hospital Clínico de Valencia	Valencia
Spain	Hospital Dr. Peset	Valencia
Sweden	ProbarE i Stockholm	Stockholm
United Kingdom	Lakeside Surgery	Corby
United Kingdom	University Hospital Coventry	Coventry
United Kingdom	Barts and The London School of Medicine and Dentistry	London
United States	Renal Associates of Baton Rouge	Baton Rouge	Louisiana
United States	Boise Kidney and Hypertension, PLLC	Boise	Idaho
United States	Clearview Medical Research, LLC	Canyon Country	California
United States	Research by Design, LLC	Chicago	Illinois
United States	Davita Clinical Research	Columbus	Georgia
United States	Davita Clinical Research	El Paso	Texas
United States	Indago Research and Health Center	Hialeah	Florida
United States	New Jersey Kidney Care, LLC	Jersey City	New Jersey
United States	Knoxville Kidney Center PLLC	Knoxville	Tennessee
United States	DaVita Clinical Research	Las Vegas	Nevada
United States	Nevada Kidney Disease and Hypertension Centers, PLLC	Las Vegas	Nevada
United States	Alma Clinical Research, Inc.	Miami	Florida
United States	Bioclinical Research Alliance, Inc.	Miami	Florida
United States	Homestead Associates in Research	Miami	Florida
United States	Panax Clinical Research	Miami Lakes	Florida
United States	Nephrology Associates, P.A.	Newark	Delaware
United States	Rancho Cucamonga Clinical Trials	Rancho Cucamonga	California
United States	Clinical Advancement Center, PLLC	San Antonio	Texas
United States	Meridian Clinical Research, LLC	Savannah	Georgia
United States	Kidney Specialists of North Houston, PLLC	Shenandoah	Texas
United States	Kidney & Hypertension Center	Victorville	California
United States	Chase Medical Research, LLC	Waterbury	Connecticut
United States	Brookview Hills Research Associates LLC	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment.		Up to 20 weeks
Secondary	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
Secondary	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

External Links

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