A Study to Test the Effect of Different Doses of Avenciguat (BI 685509) on Kidney Function in People With Chronic Kidney Disease
- Registration Number
- NCT04736628
- Lead Sponsor
- Boehringer Ingelheim
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 261
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Avenciguat 1 mg TID Avenciguat TID=ter in die (3 times a day) Avenciguat 2 mg TID Avenciguat - Avenciguat 3 mg TID Avenciguat - Placebo Placebo -
- Primary Outcome Measures
Name Time Method Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment 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. Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) measured in 10-hour urine after 20 weeks of trial treatment is reported.
Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12, and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient.
Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20).
The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Log Transformed UACR Measured in First Morning Void Urine After 20 Weeks of Trial Treatment 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. Change from baseline in log transformed UACR measured in First Morning Void urine after 20 weeks of trial treatment is reported.
Least Squares Mean (Standard error) were estimated by restricted maximum likelihood (REML)-based mixed-effect model for repeated measures (MMRM) including the fixed, categorical effects of treatment at each visit (baseline, Week 6, Week 12 and Week 20), and the continuous effect of baseline at each visit (Week 6, Week 12, and Week 20) as well as random effects of patient.
The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day. Log transformed UACR at Week 20 was log of (average of all available scheduled measurements between week 18 and week 20). The data in the Outcome Measure Data Table represent the Least Squares Mean (Standard error) at Week 20.Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment. Number of patients achieving urine albumin creatinine ratio (UACR) decreases in 10-hour urine of at least 20% from baseline after 20 weeks of trial treatment.
During the 10-hour period every time the patient urinates, and the patient collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample.Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment At baseline (Day -14 and Day -7) and at Week 20 (Day 141) after start of trial treatment. Number of patients achieving urine albumin creatinine ratio (UACR) decreases in First Morning Void urine of at least 20% from baseline after 20 weeks of trial treatment is reported. The first morning void (FMV) was the first urination after the patient woke up at their usual time to start their day.
Trial Locations
- Locations (109)
Research by Design, LLC
🇺🇸Chicago, Illinois, United States
Homestead Associates in Research
🇺🇸Miami, Florida, United States
Nevada Kidney Disease and Hypertension Centers, PLLC
🇺🇸Las Vegas, Nevada, United States
Tung Wah Hospital
🇭🇰Hong Kong, Hong Kong
Moscow 1st State Med.Univ.n.a.I.M.Sechenov
🇷🇺Moscow, Russian Federation
Prince of Wales Hospital
🇭🇰Hong Kong, Hong Kong
Instituto Nacional de Cs Médicas y Nutrición S Zubiran
🇲🇽Ciudad de México, Mexico
Clinstile S.A. de C.V.
🇲🇽México, Mexico
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Hospital Universitario Dr Jose Eleuterio Gonzalez
🇲🇽Monterrey, Mexico
ProbarE i Stockholm
🇸🇪Stockholm, Sweden
Juntendo University Urayasu Hospital
🇯🇵Chiba, Urayasu, Japan
Kyoto University Hospital
🇯🇵Kyoto, Kyoto, Japan
Hospital Raja Permaisuri Bainun
🇲🇾Ipoh, Perak, Malaysia
Nakayamadera Imai Clinic
🇯🇵Hyogo, Takarazuka, Japan
Takai Naika Clinic
🇯🇵Kanagawa, Kamakura, Japan
Stouffville Medical Centre
🇨🇦Stouffville, Ontario, Canada
Fadia El Boreky Medicine Professional
🇨🇦Waterloo, Ontario, Canada
Peking University Third Hospital
🇨🇳Beijing, China
Aarhus University Hospital
🇩🇰Aarhus N, Denmark
Herlev and Gentofte Hospital
🇩🇰Herlev, Denmark
Kurume University Hospital
🇯🇵Fukuoka, Kurume, Japan
Nihon University Itabashi Hospital
🇯🇵Tokyo, Itabashi-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
🇲🇾Selangor, Malaysia
Yaizu City Hospital
🇯🇵Shizuoka, Yaizu, Japan
Centenario Hospital Miguel Hidalgo
🇲🇽Aguascalientes, Mexico
Hospital Dr. Peset
🇪🇸Valencia, Spain
Lakeside Surgery
🇬🇧Corby, United Kingdom
Pratia MCM Krakow
🇵🇱Krakow, Poland
Clínica Universidad de Navarra
🇪🇸Pamplona, Spain
Hospital Virgen Macarena
🇪🇸Sevilla, Spain
Barts and The London School of Medicine and Dentistry
🇬🇧London, United Kingdom
Tokyo-Eki Center-building Clinic
🇯🇵Tokyo, Chuo-ku, Japan
Shinshu University Hospital
🇯🇵Nagano, Matsumoto, Japan
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Kidney & Hypertension Center
🇺🇸Victorville, California, United States
Rancho Cucamonga Clinical Trials
🇺🇸Rancho Cucamonga, California, United States
Clearview Medical Research, LLC
🇺🇸Canyon Country, 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
Panax Clinical Research
🇺🇸Miami Lakes, Florida, United States
Bioclinical Research Alliance, Inc.
🇺🇸Miami, Florida, United States
Alma Clinical Research, Inc.
🇺🇸Miami, Florida, United States
Davita Clinical Research
🇺🇸El Paso, Texas, United States
Meridian Clinical Research, LLC
🇺🇸Savannah, Georgia, United States
Boise Kidney and Hypertension, PLLC
🇺🇸Boise, Idaho, United States
DaVita Clinical Research
🇺🇸Las Vegas, Nevada, United States
Renal Associates of Baton Rouge
🇺🇸Baton Rouge, Louisiana, United States
Knoxville Kidney Center PLLC
🇺🇸Knoxville, Tennessee, United States
Kidney Specialists of North Houston, PLLC
🇺🇸Shenandoah, Texas, United States
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, Argentina
Macquarie University
🇦🇺Macquarie Park, New South Wales, Australia
Nepean Hospital
🇦🇺Kingswood, New South Wales, Australia
Renal Research, Gosford
🇦🇺Gosford, 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
Peking University People's Hospital
🇨🇳Beijing, China
Peking University First 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
Holbæk Sygehus
🇩🇰Holbæk, Denmark
Sjællands Universitetshospital
🇩🇰Roskilde, Denmark
Klinikum Region Hannover GmbH
🇩🇪Hannover, Germany
Universitätsklinikum Schleswig-Holstein, Campus Lübeck
🇩🇪Lübeck, Germany
Princess Margaret Hospital
🇭🇰Hong Kong, Hong Kong
Chubu Rosai Hospital
🇯🇵Aichi, Nagoya, Japan
Daido Hospital
🇯🇵Aichi, Nagoya, Japan
Kuana City Medical Center
🇯🇵Mie, Kuwana, Japan
The University of Tokyo Hospital
🇯🇵Tokyo, Bunkyo-ku, Japan
Kawasaki Medical School Hospital
🇯🇵Okayama, Kurashiki, Japan
Saitama Medical University Hospital
🇯🇵Saitama, Iruma-gun, Japan
Centro de Investigacion Cardiometabolica de Aguascalientes
🇲🇽Aguascalientes, Mexico
Instituto Nacional de Cardiologia Ignacio Chavez
🇲🇽Ciudad de Mexico, Mexico
Dunedin Hospital
🇳🇿Dunedin, New Zealand
P3 Research
🇳🇿Tauranga, New Zealand
Cardiovascular Centre of Malopolska
🇵🇱Chrzanow, Poland
Cent.Clin.Hosp.Med.Univ.Lodz
🇵🇱Lodz, Poland
Medicome Limited Liability Company
🇵🇱Oswiecim, Poland
Hospital Clínico de Valencia
🇪🇸Valencia, Spain
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, Portugal
Hospital Vall d'Hebron
🇪🇸Barcelona, Spain
St. Petersburg GUZ City Hospital no. 31, St. Petersburg
🇷🇺St. Petersburg, Russian Federation
Hospital de Bellvitge
🇪🇸L'Hospitalet de Llobregat, Spain
Fundación Jiménez Díaz
🇪🇸Madrid, Spain
University Hospital Coventry
🇬🇧Coventry, United Kingdom
P3 Research Kapiti
🇳🇿Paraparaumu, New Zealand
Toronto General Hospital
🇨🇦Toronto, Ontario, Canada
New Jersey Kidney Care, LLC
🇺🇸Jersey City, New Jersey, United States
Brookview Hills Research Associates LLC
🇺🇸Winston-Salem, North Carolina, United States
Clinical Advancement Center, PLLC
🇺🇸San Antonio, Texas, United States
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong