Clinical trial NCT04736628: A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic Kidney Disease
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-02-03
Enrollment: 261
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

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

Primary outcomes:
measure: Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment
timeFrame: The MMRM model is a longitudinal analysis and it incorporated UACR measurements from baseline (Week -2, Week -1, Week 0 pre-dose) and Week 6, Week 12 and Week 20. The data represent the Least Squares Mean at Week 20.
Secondary outcomes:
measure: Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment
timeFrame: 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.
measure: Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment
timeFrame: At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.
measure: Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment
timeFrame: At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment.
Other outcomes:
Locations:
city: Canyon Country
country: United States
facility: Clearview Medical Research, LLC
state: California
city: Rancho Cucamonga
country: United States
facility: Rancho Cucamonga Clinical Trials
state: California
city: Victorville
country: United States
facility: Kidney & Hypertension Center
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
city: Newark
country: United States
facility: Nephrology Associates, P.A.
state: Delaware
city: Hialeah
country: United States
facility: Indago Research and Health Center
state: Florida
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
city: Miami
country: United States
facility: Homestead Associates in Research
state: Florida
city: Miami
country: United States
facility: Bioclinical Research Alliance, Inc.
state: Florida
city: Miami
country: United States
facility: Alma Clinical Research, Inc.
state: Florida
city: Columbus
country: United States
facility: Davita Clinical Research
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Boise
country: United States
facility: Boise Kidney and Hypertension, PLLC
state: Idaho
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Baton Rouge
country: United States
facility: Renal Associates of Baton Rouge
state: Louisiana
city: Las Vegas
country: United States
facility: DaVita Clinical Research
state: Nevada
city: Las Vegas
country: United States
facility: Nevada Kidney Disease and Hypertension Centers, PLLC
state: Nevada
city: Jersey City
country: United States
facility: New Jersey Kidney Care, LLC
state: New Jersey
city: Winston-Salem
country: United States
facility: Brookview Hills Research Associates LLC
state: North Carolina
city: Knoxville
country: United States
facility: Knoxville Kidney Center PLLC
state: Tennessee
city: El Paso
country: United States
facility: Davita Clinical Research
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: Shenandoah
country: United States
facility: Kidney Specialists of North Houston, PLLC
state: Texas
city: Caba
country: Argentina
facility: STAT Research
city: Caba
country: Argentina
facility: CEDIC - Centro de Investigacion Clinica
city: Caba
country: Argentina
facility: CEMIC
city: Cordoba
country: Argentina
facility: Instituto Privado de Investigaciones Clínica Córdoba S.A.
city: Mar del Plata
country: Argentina
facility: Centro de Investigaciones Médicas Mar del Plata
city: Mar del Plata
country: Argentina
facility: Instituto de Investigaciones Clinicas Mar del Plata
city: Rosario
country: Argentina
facility: Instituto Médico Catamarca - IMEC
city: Santa Fe
country: Argentina
facility: CEDIR Santa Fe
city: Sarandi
country: Argentina
facility: CEREHA S.A.- Centro de Estudios Renales e Hipertensión Arterial
city: Gosford
country: Australia
facility: Renal Research, Gosford
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: Macquarie Park
country: Australia
facility: Macquarie University
state: New South Wales
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Health
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: Red Deer
country: Canada
facility: CARe Clinic
state: Alberta
city: Stouffville
country: Canada
facility: Stouffville Medical Centre
state: Ontario
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Albion Finch Medical Centre
state: Ontario
city: Waterloo
country: Canada
facility: Fadia El Boreky Medicine Professional
state: Ontario
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Chengdu
country: China
facility: People's Hospital of Sichuan Province
city: Chongqing
country: China
facility: Second Affiliated Hospital Chongqing Medical University
city: Xuancheng
country: China
facility: The People's Hospital Of Xuancheng City
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Herlev and Gentofte Hospital
city: Holbæk
country: Denmark
facility: Holbæk Sygehus
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital
city: Hannover
country: Germany
facility: Klinikum Region Hannover GmbH
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
city: Hong Kong
country: Hong Kong
facility: Prince of Wales Hospital
city: Hong Kong
country: Hong Kong
facility: Princess Margaret Hospital
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital
city: Hong Kong
country: Hong Kong
facility: Tung Wah Hospital
city: Aichi, Nagoya
country: Japan
facility: Chubu Rosai Hospital
city: Aichi, Nagoya
country: Japan
facility: Daido Hospital
city: Chiba, Urayasu
country: Japan
facility: Juntendo University Urayasu Hospital
city: Fukuoka, Kurume
country: Japan
facility: Kurume University Hospital
city: Hyogo, Takarazuka
country: Japan
facility: Nakayamadera Imai Clinic
city: Kanagawa, Kamakura
country: Japan
facility: Takai Naika Clinic
city: Kyoto, Kyoto
country: Japan
facility: Kyoto University Hospital
city: Mie, Kuwana
country: Japan
facility: Kuana City Medical Center
city: Nagano, Matsumoto
country: Japan
facility: Shinshu University Hospital
city: Okayama, Kurashiki
country: Japan
facility: Kawasaki Medical School Hospital
city: Saitama, Iruma-gun
country: Japan
facility: Saitama Medical University Hospital
city: Shizuoka, Yaizu
country: Japan
facility: Yaizu City Hospital
city: Tokyo, Bunkyo-ku
country: Japan
facility: The University of Tokyo Hospital
city: Tokyo, Chuo-ku
country: Japan
facility: Tokyo-Eki Center-building Clinic
city: Tokyo, Itabashi-ku
country: Japan
facility: Nihon University Itabashi Hospital
city: Cheras, Kuala Lumpur
country: Malaysia
facility: University Kebangsaan Malaysia
city: Ipoh, Perak
country: Malaysia
facility: Hospital Raja Permaisuri Bainun
city: Kelantan
country: Malaysia
facility: Universiti Sains Malaysia Hospital
city: Kuala Lumpur
country: Malaysia
facility: University of Malaya Medical Centre
city: Selangor
country: Malaysia
facility: Hospital Selayang
city: Aguascalientes
country: Mexico
facility: Centro de Investigacion Cardiometabolica de Aguascalientes
city: Aguascalientes
country: Mexico
facility: Centenario Hospital Miguel Hidalgo
city: Ciudad de Mexico
country: Mexico
facility: Instituto Nacional de Cardiologia Ignacio Chavez
city: Ciudad de México
country: Mexico
facility: Instituto Nacional de Cs Médicas y Nutrición S Zubiran
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: México
country: Mexico
facility: Clinstile S.A. de C.V.
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Paraparaumu
country: New Zealand
facility: P3 Research Kapiti
city: Tauranga
country: New Zealand
facility: P3 Research
city: Chrzanow
country: Poland
facility: Cardiovascular Centre of Malopolska
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Lodz
country: Poland
facility: Cent.Clin.Hosp.Med.Univ.Lodz
city: Oswiecim
country: Poland
facility: Medicome Limited Liability Company
city: Aveiro
country: Portugal
facility: ULS da Região de Aveiro
city: Carnaxide
country: Portugal
facility: CHLO, EPE - Hospital de Santa Cruz
city: Lisboa
country: Portugal
facility: ULS de Santa Maria, E.P.E
city: Porto
country: Portugal
facility: Centro Hospitalar Universitário São João,EPE
city: Moscow
country: Russian Federation
facility: Moscow 1st State Med.Univ.n.a.I.M.Sechenov
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg GUZ City Hospital no. 31, St. Petersburg
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: L'Hospitalet de Llobregat
country: Spain
facility: Hospital de Bellvitge
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital Dr. Peset
city: Stockholm
country: Sweden
facility: ProbarE i Stockholm
city: Corby
country: United Kingdom
facility: Lakeside Surgery
city: Coventry
country: United Kingdom
facility: University Hospital Coventry
city: London
country: United Kingdom
facility: Barts and The London School of Medicine and Dentistry
Study officials:
References: