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

NCT04750577 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 1366-00052020-002929-28
• Study Type: interventional
• Target: 243
• Locations: 16 countries
• Sites: 78

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (UACR) Measured in 10-hour Urine After 20 Weeks of Trial Treatment

  Change from baseline in log transformed Urine Albumin Creatinine Ratio (UACR) after 20 weeks is reported. As soon as the First Morning Void sample was collected the clock starts for the 10-hour urine collection. During the 10-hour period every time the patient urinates, they collected their urine into a provided container. An aliquot of this urine was taken and used as the 10-hour UACR sample. Least Square Means and Standard error were estimated by restricted maximum likelihood based Mixed-effect Model for Repeated Measures ((REML)-based 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 Least Squares Mean (Standard error) at Week 20 is reported.

  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.

Secondary Outcomes (3)

• Change From Baseline in Log Transformed Urine Albumin Creatinine Ratio (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.

• Number of Patients Achieving UACR Decreases in 10-hour Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment

  Baseline (day -14 and -7) and week 20 (day 141).

• Number of Patients Achieving UACR Decreases in First Morning Void Urine of at Least 20% From Baseline After 20 Weeks of Trial Treatment

  Baseline (day -14 and -7) and week 20 (day 141).

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Drug: Placebo matching BI 685509

BI 685509 1 mg TID

EXPERIMENTAL

Drug: BI 685509

BI 685509 2 mg TID

EXPERIMENTAL

Low dose followed by up-titration to medium dose.

Drug: BI 685509

BI 685509 3 mg TID

EXPERIMENTAL

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

Drug: BI 685509

Interventions

Placebo matching BI 685509 DRUG

film-coated tablet

Placebo

BI 685509 DRUG

film-coated tablet

Also known as: Avenciguat

BI 685509 1 mg TID; BI 685509 2 mg TID; BI 685509 3 mg TID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Male or female patients aged ≥ 18 years at time of consent.
• 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.
• 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.
• 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.
• 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.
• Glycated Haemoglobin (HbA1c) \< 10.0% at Visit 1 measured by the central laboratory.

You may not qualify if:

• 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.
• Any clinically relevant laboratory value from screening until start of trial treatment, which in the investigator's judgement puts the patient at additional risk.
• 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).
• 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).
• 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.
• 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.

Sponsors & Collaborators

• Boehringer Ingelheim: lead

Study Sites (78)

Kidney & Hypertension Center

Victorville, California, 92395, United States

Location

Chase Medical Research, LLC

Waterbury, Connecticut, 06708, United States

Location

Indago Research and Health Center

Hialeah, Florida, 33012, United States

Location

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Davita Clinical Research

Columbus, Georgia, 31904, United States

Location

Meridian Clinical Research, LLC

Savannah, Georgia, 31406, United States

Location

Research by Design, LLC

Chicago, Illinois, 60643, United States

Location

DaVita Clinical Research

Las Vegas, Nevada, 89128, United States

Location

Total Renal Research

The Bronx, New York, 10461, United States

Location

Brookview Hills Research Associates LLC

Winston-Salem, North Carolina, 27103, United States

Location

Knoxville Kidney Center PLLC

Knoxville, Tennessee, 37923, United States

Location

DaVita Clinical Research

Houston, Texas, 77054, United States

Location

Texas Institute for Kidney and Endocrine Disorders

Lufkin, Texas, 75904, United States

Location

Clinical Advancement Center, PLLC

San Antonio, Texas, 78212, United States

Location

DaVita Clinical Research

San Antonio, Texas, 78240, United States

Location

Kidney Specialists of North Houston, PLLC

Shenandoah, Texas, 77384, United States

Location

Tidewater Kidney Specialists

Norfolk, Virginia, 23510, United States

Location

CEDIC - Centro de Investigacion Clinica

CABA, C1060ABN, Argentina

Location

Instituto Médico Especializado

Capital Federal, C1405BCH, Argentina

Location

Instituto Privado de Investigaciones Clínica Córdoba S.A.

Córdoba, X5000AAW, Argentina

Location

Centro de Investigaciones Médicas Mar del Plata

Mar del Plata, B7600FYK, Argentina

Location

Instituto Médico Catamarca - IMEC

Rosario, S2000AJU, Argentina

Location

CEREHA S.A.- Centro de Estudios Renales e Hipertensión Arterial

Sarandí, B1872EEB, Argentina

Location

Renal Research, Gosford

Gosford, New South Wales, 2250, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

Macquarie University

Macquarie Park, New South Wales, 2109, Australia

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

CARe Clinic

Red Deer, Alberta, T4P 1K4, Canada

Location

Albion Finch Medical Centre

Toronto, Ontario, M9V 4B4, Canada

Location

Fadia El Boreky Medicine Professional

Waterloo, Ontario, N2J 1C4, Canada

Location

Peking University First Hospital

Beijing, 100034, China

Location

Peking University Third Hospital

Beijing, 100191, China

Location

Second Affiliated Hospital Chongqing Medical University

Chongqing, 400016, China

Location

People's Hospital of Sichuan Province

Sichuan, 610031, China

Location

Aarhus University Hospital

Aarhus N, 8200, Denmark

Location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Sjællands Universitetshospital

Roskilde, 4000, Denmark

Location

Prince of Wales Hospital

Hong Kong, 999077, Hong Kong

Location

Queen Mary Hospital

Hong Kong, 999077, Hong Kong

Location

Tung Wah Hospital

Hong Kong, Hong Kong

Location

Chubu Rosai Hospital

Aichi, Nagoya, 455-8530, Japan

Location

Daido Hospital

Aichi, Nagoya, 457-8511, Japan

Location

Kurume University Hospital

Fukuoka, Kurume, 830-0011, Japan

Location

Nakayamadera Imai Clinic

Hyogo, Takarazuka, 665-0861, Japan

Location

Takai Naika Clinic

Kanagawa, Kamakura, 247-0056, Japan

Location

Kawasaki Medical School Hospital

Okayama, Kurashiki, 701-0192, Japan

Location

Osaka General Medical Center

Osaka, Osaka, 558-8558, Japan

Location

OCROM Clinic

Osaka, Suita, 565-0853, Japan

Location

Saitama Medical University Hospital

Saitama, Iruma-gun, 350-0495, Japan

Location

The University of Tokyo Hospital

Tokyo, Bunkyo-ku, 113-8655, Japan

Location

Tokyo-Eki Center-building Clinic

Tokyo, Chuo-ku, 103-0027, Japan

Location

ToCROM Clinic

Tokyo, Shinjyuku-ku, 160-0008, Japan

Location

University Kebangsaan Malaysia

Cheras, Kuala Lumpur, 56000, Malaysia

Location

Universiti Sains Malaysia Hospital

Kelantan, 16150, Malaysia

Location

University of Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Hospital Selayang

Kuala Selangor, 68100, Malaysia

Location

Hospital Cardiologica Aguascalientes

Aguascalientes, 20230, Mexico

Location

Centenario Hospital Miguel Hidalgo

Aguascalientes, 20259, Mexico

Location

Clinstile S.A. de C.V.

México, 06700, Mexico

Location

Hospital Universitario Dr Jose Eleuterio Gonzalez

Monterrey, 64460, Mexico

Location

Albert SchweitzerZiekenhuis

Dordrecht, 3318 AT, Netherlands

Location

Universitair Medisch Centrum Utrecht

GA Utrecht, 3508, Netherlands

Location

P3 Research Kapiti

Paraparaumu, 5032, New Zealand

Location

P3 Research

Tauranga, 3110, New Zealand

Location

SPECDERM Poznanska General Partnership

Bialystok, 15-375, Poland

Location

Pratia MCM Krakow

Krakow, 30-510, Poland

Location

Medicome Limited Liability Company

Oświęcim, 32-600, Poland

Location

NBR Polska

Warsaw, 00710, Poland

Location

ULS da Região de Aveiro

Aveiro, 3810-164, Portugal

Location

APDP - Associação Protectora dos Diabéticos de Portugal

Lisbon, 1250-189, Portugal

Location

Hospital A Coruña

A Coruña, 15006, Spain

Location

Hospital Vall d'Hebron

Barcelona, 08035, Spain

Location

Hospital Virgen Macarena

Seville, 41009, Spain

Location

Hospital Clínico de Valencia

Valencia, 46010, Spain

Location

University Hospital Coventry

Coventry, CV2 2DX, United Kingdom

Location

Barts and The London School of Medicine and Dentistry

London, EC1M 6BQ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 38795055 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Diabetic Nephropathies

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Results Point of Contact

• Title: Boehringer Ingelheim, Call Center
• Organization: Boehringer Ingelheim

clintriage.rdg@boehringer-ingelheim.com

1-800-243-0127

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Multicentre, randomised, double-blind (within dose groups), parallel, placebo-controlled trial. Patients will be randomised equally into one of three parallel dose groups, and in each dose group to treatment either with BI 685509 or matching placebo in a 3:1 ratio.

Study Record Dates

• First Submitted: February 9, 2021
• First Posted: February 11, 2021
• Study Start: April 27, 2021
• Primary Completion: November 30, 2022
• Study Completion: December 27, 2022
• Last Updated: July 23, 2024
• Results First Posted: July 23, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: One year after the approval has been granted by major Regulatory Authorities and after the primary manuscript has been accepted for publication, or after termination of the development program.
• Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by the sponsor and/or the independent review panel, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a legal agreement.

Locations

CN (4); ES (4); MY (4); JP (12); GB (2); PL (4); CA (3); NZ (2); AR (6); DK (3); ME (4); HK (3); NL (2); US (17); AU (6); PT (2)