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)
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
Panax Clinical Research
🇺🇸Miami Lakes, 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
Scroll for more (99 remaining)Clearview Medical Research, LLC🇺🇸Canyon Country, California, United States