Clinical trial NCT04750577: A Study to Test the Effect of Different Doses of BI 685509 on Kidney Function in People With Diabetic 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 Diabetic Kidney Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diabetic Nephropathies
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2021-02-11
Enrollment: 243
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. 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.
2. Male or female patients aged ≥ 18 years at time of consent.
3. 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.
4. Urine Albumin Creatinine Ratio (UACR) ≥ 200 and \< 3,500 mg/g in spot urine (midstream urine sample) by central laboratory analysis at Visit 1.
5. 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.
6. 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.
7. 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.
8. Glycated Haemoglobin (HbA1c) \< 10.0% at Visit 1 measured by the central laboratory.

Further inclusion criteria apply.

Exclusion criteria:

1. 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.
2. Any clinically relevant laboratory value from screening until start of trial treatment, which in the investigator's judgement puts the patient at additional risk.
3. 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).
4. 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).
5. 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.
6. Planned start of chronic renal replacement therapy during the trial or end stage renal disease before start of trial treatment.
7. Known history of moderate or severe symptomatic orthostatic dysregulation as judged by the investigator before start of trial treatment.
8. 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 and Week -1) 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 Urine Albumin Creatinine Ratio (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: Baseline (day -14 and -7) and week 20 (day 141).
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: Baseline (day -14 and -7) and week 20 (day 141).
Other outcomes:
Locations:
city: Victorville
country: United States
facility: Kidney & Hypertension Center
state: California
city: Waterbury
country: United States
facility: Chase Medical Research, LLC
state: Connecticut
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: Columbus
country: United States
facility: Davita Clinical Research
state: Georgia
city: Savannah
country: United States
facility: Meridian Clinical Research, LLC
state: Georgia
city: Chicago
country: United States
facility: Research by Design, LLC
state: Illinois
city: Las Vegas
country: United States
facility: DaVita Clinical Research
state: Nevada
city: Bronx
country: United States
facility: Total Renal Research
state: New York
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: Houston
country: United States
facility: DaVita Clinical Research
state: Texas
city: Lufkin
country: United States
facility: Texas Institute for Kidney and Endocrine Disorders
state: Texas
city: San Antonio
country: United States
facility: Clinical Advancement Center, PLLC
state: Texas
city: San Antonio
country: United States
facility: DaVita Clinical Research
state: Texas
city: Shenandoah
country: United States
facility: Kidney Specialists of North Houston, PLLC
state: Texas
city: Norfolk
country: United States
facility: Tidewater Kidney Specialists
state: Virginia
city: Caba
country: Argentina
facility: CEDIC - Centro de Investigacion Clinica
city: Capital Federal
country: Argentina
facility: Instituto Médico Especializado
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: Rosario
country: Argentina
facility: Instituto Médico Catamarca - IMEC
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: Red Deer
country: Canada
facility: CARe Clinic
state: Alberta
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 Third Hospital
city: Chongqing
country: China
facility: Second Affiliated Hospital Chongqing Medical University
city: Sichuan
country: China
facility: People's Hospital of Sichuan Province
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Roskilde
country: Denmark
facility: Sjællands Universitetshospital
city: Hong Kong
country: Hong Kong
facility: Prince of Wales 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: 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: Okayama, Kurashiki
country: Japan
facility: Kawasaki Medical School Hospital
city: Osaka, Osaka
country: Japan
facility: Osaka General Medical Center
city: Osaka, Suita
country: Japan
facility: OCROM Clinic
city: Saitama, Iruma-gun
country: Japan
facility: Saitama Medical University 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, Shinjyuku-ku
country: Japan
facility: ToCROM Clinic
city: Cheras, Kuala Lumpur
country: Malaysia
facility: University Kebangsaan Malaysia
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: Hospital Cardiologica Aguascalientes
city: Aguascalientes
country: Mexico
facility: Centenario Hospital Miguel Hidalgo
city: Monterrey
country: Mexico
facility: Hospital Universitario Dr Jose Eleuterio Gonzalez
city: México
country: Mexico
facility: Clinstile S.A. de C.V.
city: Dordrecht
country: Netherlands
facility: Albert SchweitzerZiekenhuis
city: GA Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Paraparaumu
country: New Zealand
facility: P3 Research Kapiti
city: Tauranga
country: New Zealand
facility: P3 Research
city: Bialystok
country: Poland
facility: SPECDERM Poznanska General Partnership
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Oswiecim
country: Poland
facility: Medicome Limited Liability Company
city: Warsaw
country: Poland
facility: NBR Polska
city: Aveiro
country: Portugal
facility: ULS da Região de Aveiro
city: Lisboa
country: Portugal
facility: APDP - Associação Protectora dos Diabéticos de Portugal
city: A Coruña
country: Spain
facility: Hospital A Coruña
city: Barcelona
country: Spain
facility: Hospital Vall d'Hebron
city: Sevilla
country: Spain
facility: Hospital Virgen Macarena
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
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: