Clinical trial NCT04661917: A Trial to Learn More About How BAY2327949 Works and How Safe it is in Patients Whose Kidneys Are Damaged Due to High Blood Sugar Levels or High Blood Pressures, and With a Further Disease of the Heart or the Blood Vessels.
Official title: A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Efficacy and Safety of BAY 2327949 in Patients With Chronic Kidney Disease (eGFR Range From 25 to 60 mL/Min/1.73 m²) Due to Type 2 Diabetes or Hypertension and at Least One Cardiovascular Comorbidity
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Chronic Kidney Disease
Diabetic Kidney Disease
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-12-10
Enrollment: 0
Sex: ALL
Minimum age (years): 45
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: In people with type 2 diabetes (T2D), the body makes insulin, but cannot use it well. This results in high blood sugar levels causing damage to the blood vessels inside the kidneys.

High blood pressure is a common condition that can cause damage to the blood vessels and heart if it is untreated. High blood pressure is also known as hypertension.

Patients with type 2 diabetes (T2D) or high blood pressure are at a higher risk of having chronic kidney disease (CKD). In people with CKD, the kidneys become damaged and do not work as they should. Over time, the function of the kidney declines more, and this can lead to the requirement for dialysis or kidney transplantation. Most people with CKD are also at risk of heart conditions, such as heart attack or stroke.

In this trial, the researchers want to learn if BAY2327949 reduces the amount of protein in the participants' urine. Protein in the urine is one of the signs of CKD. The researchers will compare the effects of BAY2327949 to a placebo. A placebo looks like the study drug but does not have any medicine in it. BAY2327949 is assumed to increase the blood flow through the kidneys, which may slow down the worsening of the disease. The researchers will use a placebo to learn if the changes seen in the participants are due to BAY2327949 or if the results could be due to chance.

This trial will include about 120 men and women over the age of 45 who have CKD. The participants will have T2D or high blood pressure, and a further disease of the heart or blood vessels.

During the trial, the participants will take either BAY2327949 or a placebo once a day for 28 days. The participants will visit their trial site about 9 times during the trial, and need to provide urine samples to check the participants' CKD symptoms. At the visits, the doctors will ask them if they have any health problems. They will also take blood samples to perform laboratory assessments.


Eligibility criteria: Inclusion Criteria:

* A clinical diagnosis of chronic kidney disease (CKD) with estimated glomerular filtration rate (eGFR) ≥ 25 mL/min/1.73 m\^2 but ≤ 60 mL/min/1.73 m\^2 (estimated using the CKD-EPI \[Epidemiology Collaboration\] equation) as assessed during Visit 1, and albuminuria (as measured by urine albumin-to-creatinine ratio \[UACR\]) in the range of ≥ 30 but ≤ 3000 mg/g, based on the first assessment for Visit 1.
* CKD with a clinical cause of either T2D or hypertension: -- if T2D is the clinical cause, history of type 2 diabetes mellitus as defined by the American Diabetes Association (on treatment with glucose-lowering medications and/or insulin) for at least 2 years before randomization and on a stable therapy with sodium-glucose transport protein 2 (SGLT2) inhibitor for at least 3 months before randomization; -- if hypertension is the clinical cause, patients must have a history of systolic blood pressure (BP) values ≥ 140 mmHg and/or diastolic BP values ≥ 90 mmHg, and on hypertension medication for at least 5 years before randomization.
* Stable treatment with either angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) at the maximal tolerated labelled daily dose and otherwise stable antihypertensive treatment both for at least 3 months before randomization. If taking an SGLT2 inhibitor, the participant must be on stable treatment for at least 3 months before randomization without any planned changes in dosing during the study period. All treatments must be expected to remain stable over the study period without any planned dose adjustments.
* Body mass index within the range of 18-38 kg/m\^2 as evaluated for Visit 1.
* Male participants must agree to use barrier contraception (condoms). Female participants must be of non-child-bearing potential.

Exclusion Criteria:

* Known non-diabetic or non-hypertensive renal disease (e.g. autosomal dominant polycystic kidney disease or autosomal recessive polycystic kidney disease, bilateral clinically relevant renal artery stenosis, lupus nephritis, or ANCA-associated vasculitis, or any other secondary glomerulonephritis).
* Clinical diagnoses of heart failure and persistent symptoms (NYHA \[New York Heart Association\] class III - IV), or hospitalization for worsening heart failure in the last 3 months prior to signing the informed consent form (ICF).
* Uncontrolled hypertension indicated by \>160 mmHg systolic BP or ≥100 mmHg diastolic BP at Visit 1 or Visit 2 or at any unscheduled visit before randomization.
* History of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism, or pheochromocytoma); stroke, transient ischemic cerebral attack, acute coronary syndrome in the last 3 months prior to signing the ICF.
* Dialysis for acute renal failure within the previous 6 months prior to signing the ICF.
* Renal allograft in place or a scheduled kidney transplant within the next 18 weeks from signing the ICF (being on a waiting list does not exclude the participant).
* Hepatic insufficiency classified as Child-Pugh B or C or other significant liver disease (e.g., acute hepatitis, chronic active hepatitis, cirrhosis as indicated by e.g. AST/ALT \>3x ULN).
* Active malignancy. Previous malignancies are allowed if there is a 5-year remission- and treatment-free time before signing the ICF.
* Any surgical or medical condition, which in the opinion of the investigator, may place the participant at higher risk from his/her participation in the study, or is likely to prevent the participant from complying with the requirements of the study or completing the study.
* For participants without diabetes: receiving off-label treatment with an SGLT2 inhibitor.
* Indication for immunosuppressants, receiving cytotoxic therapy, immunosuppressive therapy, or other immunotherapy within 6 months prior to signing ICF.
* Combination use of an ACE inhibitor and ARB within 3 months prior to signing ICF.
* Concomitant therapy with drugs that strongly induce or inhibit CYP3A4 (cytochrome P-450 3A4), or that are inhibitors of P-gp (P-glucoprotein).
* Planned change of concomitant medications or dose adjustments during participation in this study.
* Participation in another clinical study with treatment with another investigational product 90 days prior to signing ICF.
* HbA1c \> 11% at Visit 1.

Primary outcomes:
measure: Change from baseline in urine albumin-to-creatinine ratio (UACR) to the end of treatment (Visit 6)
timeFrame: Baseline and Visit 6 (28 days)
Secondary outcomes:
measure: Frequency of treatment-emergent adverse events (TEAEs)
timeFrame: From the first treatment with the study intervention until 7 days after the last dose, up to 5 weeks
Other outcomes:
Locations:
city: Linz
country: Austria
facility: Konventhospital Barmherzige Brüder Linz
state: Oberösterreich
city: Graz
country: Austria
facility: Medizinische Universität Graz
state: Steiermark
city: Feldkirch
country: Austria
facility: Landeskrankenhaus Feldkirch
state: Vorarlberg
city: St. Pölten
country: Austria
facility: Universitätsklinikum St. Pölten
city: Wien
country: Austria
facility: Zentrum f. klinische Studien Dr. Hanusch GmbH
city: Wien
country: Austria
facility: Universitätsklinikum AKH Wien
city: Wien
country: Austria
facility: Klinik Hietzing
city: Aarhus N
country: Denmark
facility: Aarhus Universitetshospital, Skejby
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus Esbjerg
city: Herning
country: Denmark
facility: Regionshospitalet Herning
city: Hillerød
country: Denmark
facility: Nordsjællands Hospital
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital
city: Odense C
country: Denmark
facility: Odense Universitetshospital
city: Kuopio
country: Finland
facility: Health Step Finland Oy
city: Lahti
country: Finland
facility: Päijät-Hämeen keskussairaala
city: Oulu
country: Finland
facility: Oulun yliopistollinen sairaala
city: Seinäjoki
country: Finland
facility: Seinäjoen keskussairaala
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala, kantasairaala
city: Amsterdam
country: Netherlands
facility: Academisch Medisch Centrum (AMC)
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, Locatie Dordwijk
city: Eindhoven
country: Netherlands
facility: Maxima Medisch Centrum, locatie Eindhoven
city: Zwijndrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis, locatie Zwijndrecht
city: Hamar
country: Norway
facility: AKTIMED Helse AS
city: Hamar
country: Norway
facility: Sykehuset Innlandet HF Hamar
city: Oslo
country: Norway
facility: Oslo Universitetssykehus HF, Rikshospitalet
city: Skedsmokorset
country: Norway
facility: Skedsmo Medisinske Senter
city: Stavanger
country: Norway
facility: Stavanger Helseforskning AS
city: Trondheim
country: Norway
facility: St. Olavs Hospital HF
city: Göteborg
country: Sweden
facility: Carlanderska Sjukhuset
city: Lund
country: Sweden
facility: ProbarE
city: Rättvik
country: Sweden
facility: Dalecarlia Clinical Research
city: Stockholm
country: Sweden
facility: Center For Diabetes, Academic Specialist Center
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: St. Gallen
country: Switzerland
facility: Kantonsspital St. Gallen
state: Sankt Gallen
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois (CHUV)
state: Vaud
city: Bern
country: Switzerland
facility: Inselspital Universitätsspital Bern
Study officials:
References: