Study on the Safety of the Drug Runcaciguat and How Well it Works When Given at the Highest Dose as Tolerated by Individual Patient Whose Kidneys Are Not Working Properly and Suffering at the Same Time From High Blood Sugar and/or High Blood Pressure and a Disease of the Heart and the Blood Vessels.

NCT ID: NCT04507061

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 243 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-09-01
• Study Completion Date: 2022-04-05

Brief Summary

Researchers in this study want to learn more about the safety of the drug runcaciguat and how well it works when given at the highest dose as tolerated by the individual patient whose kidneys are not working properly and suffering at the same time from high blood sugar and/or high blood pressure and a disease of the heart and the blood vessels. Runcaciguat is a new drug under development for the improvement of kidney function. It works by activating proteins that helps to dilate blood vessels, including vessels in the kidneys. This can improve blood flow in kidney and may slow down the progression of kidney disease. This dilative effect can also influence the heart rate and blood pressure. Researchers also wants to find the best dose of the drug during the study.

Participants in this study will receive either runcaciguat or placebo tablets every morning for 8 weeks. A placebo looks like the study drug but does not have any active medicine in it. On a weekly basis, the dose of the runcaciguat will be increased step by step. In total, participants will visit the doctors about 10 times, and the observation will last for about 16 weeks. Blood and urine samples will collected from the participants.

Conditions

Chronic Kidney Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

runcaciguat

Participant randomized to this arm will be up-titrated. A 30-day safety follow up will be performed after end of treatment or after early discontinuation from the study.

Group Type: EXPERIMENTAL

runcaciguat

Intervention Type: DRUG

Titrated dose of active dose 1, dose 2, dose 3, dose 4 of runcaciguat will be administered orally once a day.

Placebo

Participant randomized to this arm will be sham-titrated. A 30-day safety follow up will be performed after end of treatment or after early discontinuation from the study.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Sham-titrated dose of matching placebo will be administered orally once a day.

Interventions

runcaciguat

Titrated dose of active dose 1, dose 2, dose 3, dose 4 of runcaciguat will be administered orally once a day.

Intervention Type: DRUG

Placebo

Sham-titrated dose of matching placebo will be administered orally once a day.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Age - Participant must be ≥ 45 of age inclusive, at the time of signing the informed consent.

Type of Participant and Disease Characteristics

• Participants who have:

• history of any of the following:

• 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, and/or;
• diagnosis of hypertension (defined as systolic blood pressure [BP] values ≥ 140 mmHg and/or diastolic BP values ≥90 mmHg) and on hypertension medication for at least 5 years;
• established atherosclerotic cardiovascular disease (e.g. coronary artery disease, peripheral arterial disease, cerebrovascular disease) or heart failure;
• a clinical diagnosis of chronic kidney disease (CKD) based on all of the following criteria:

• (estimated) glomerular filtration rate (eGFR) ≥ 25 mL/min/1.73 m^2 but ≤ 60 mL/min/1.73 m^2 (acc. Percentage of decrease in eGFR [CKD EPI]);
• persistent high albuminuria defined as urine albumin-to-creatinine ratio [UACR] of between 30 mg/g and 3000 mg/g in 2 first morning void samples (collected at least 1 week apart);
• Stable treatment with angiotensin-converting enzyme inhibitor (ACEi) or angiotensin-receptor blocker (ARB) for the participant maximum tolerated labelled daily dose and otherwise stable antihypertensive treatment both for at least 3 months before randomization, without any adjustments to this therapy for at least 4 weeks prior to randomization;
• Diabetes patients that are on SGLT2-inhibitor (SGLT: sodium glucose transport protein) have to be on stable treatment for at least 3 months before Screening visit.

Exclusion Criteria

• Known non-diabetic and non-hypertension related renal diseases as autosomal dominant polycystic kidney disease, bilateral clinically relevant renal artery stenosis, lupus nephritis, or ANCA-associated vasculitis, IgA nephropathy without hypertension, or any other secondary glomerulonephritis;
• Clinical diagnoses of heart failure and persistent symptoms (New York Heart Association (NYHA class III - IV);
• Uncontrolled hypertension indicated by >160 mmHg systolic BP or ≥ 100 mmHg diastolic BP;
• History of secondary hypertension (i.e., renal artery stenosis, primary aldosteronism, or pheochromocytoma);
• Stroke, transient ischemic cerebral attack, acute coronary syndrome, or hospitalization for worsening heart failure, in the last 3 months prior to the planned randomization;
• Dialysis for acute renal failure within the previous 6 months prior to the planned randomization;
• Renal allograft in place or a scheduled kidney transplant within the next 18 weeks (being on a waiting list does not exclude the subject);
• 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. aspartate aminotransferase [AST] or Alanine aminotransferase [ALT] >3x upper limit of norm [ULN]);
• Active malignancy other than treated squamous cell, carcinoma in situ, or basal cell carcinoma of the skin Prior/Concomitant Therapy;
• Any surgical or medical condition, which in the opinion of the investigator, may place the patient at higher risk from his/her participation in the study, or is likely to prevent the patient from complying with the requirements of the study or completing the study including but not limited to:

1. History of active inflammatory bowel disease within the last 6 months before randomization;

2. Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;

3. Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last 6 months before randomization;

4. Pancreatic injury or pancreatitis within the last 6 months before randomization;

• Non diabetic patients treated with SGLT-2 (SGLT:sodium glucose transport protein) inhibitors;
• Combination use of ACEi and ARB within 3 months prior to randomization;
• Concomitant therapy with nitrates, PDE5 inhibitors including nonspecific inhibitors (e.g. dipyridamole and theophylline), soluble guanylate cyclase [sGC] stimulators, renin inhibitors (within 4 weeks prior to randomization);
• Participation in another clinical study or treatment with another investigational product 90 days prior to randomization;
• Previous randomization in this study;
• hemoglobin A1c (HbA1c) >11%;

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bayer

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bayer Study Director

Role: STUDY_DIRECTOR

Bayer

Locations

Medizinische Universität Innsbruck

Innsbruck, , Austria

Klinik Landstraße - Krankenhaus Rudolfstiftung

Vienna, , Austria

Zentrum f. klinische Studien Dr. Hanusch GmbH

Vienna, , Austria

Universitätsklinikum AKH Wien

Vienna, , Austria

Klinik Hietzing

Vienna, , Austria

OL Vrouwziekenhuis - Campus Aalst

Aalst, , Belgium

Hôpital Erasme/Erasmus Ziekenhuis

Bruxelles - Brussel, , Belgium

UZ Gent

Ghent, , Belgium

UZ Leuven Gasthuisberg

Leuven, , Belgium

Med Centre Diamedical 2013

Dimitrovgrad, , Bulgaria

Multiprofile Hospital for Active Treatment Medline Clinic

Plovdiv, , Bulgaria

MHAT Sveta Karidad

Plovdiv, , Bulgaria

MHAT Dr. Bratan Shukerov AD

Smolyan, , Bulgaria

MHAT "Knyaginya Klementina - Sofia"EAD

Sofia, , Bulgaria

MC Kalimat

Sofia, , Bulgaria

MCOMH Preventsia-2000

Stara Zagora, , Bulgaria

Region Nordjylland | Aalborg University Hospital - Cardiology Department

Aalborg, , Denmark

Steno Diabetes Center Copenhagen

Herlev, , Denmark

Regionshospitalet Gødstrup

Herning, , Denmark

Holbæk Sygehus

Holbæk, , Denmark

Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme

Kolding, , Denmark

Odense Universitetshospital, Endokrinologisk Afd. M

Odense C, , Denmark

StudyCor Oy

Jyväskylä, , Finland

Diagnos Klaukkalan Lääkäriasema

Klaukkala, , Finland

Satucon / Kuopion Työterveys

Kuopio, , Finland

Omena Terveys Oy

Seinäjoki, , Finland

Turun yliopistollinen keskussairaala

Turku, , Finland

Klinikum der Universität Würzburg

Würzburg, Bavaria, Germany

Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)

Bad Oeynhausen, North Rhine-Westphalia, Germany

DaVita Clinical Research Deutschland GmbH

Düsseldorf, North Rhine-Westphalia, Germany

InnoDiab Forschung GmbH

Essen, North Rhine-Westphalia, Germany

Medamed Studienambulanz GmbH

Leipzig, Saxony, Germany

Barzilai Medical Center | Nephrology & Hypertension Dept.

Ashkelon, , Israel

Lady Davis Carmel Medical Center

Haifa, , Israel

Edith Wolfson Medical Center

Holon, , Israel

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, , Israel

Health Corporation of Galilee Medical Center

Nahariya, , Israel

Clalit Health Services Rabin Medical Center-Beilinson Campus

Petah Tikva, , Israel

Chaim Sheba Medical Center

Ramat Gan, , Israel

Poriya Medical Center | Nephrology and Hypertension Dept.

Tiberius, , Israel

A.O.U. Luigi Vanvitelli

Napoli, Campania, Italy

A.O.U. di Bologna Policlinico S.Orsola Malpighi

Bologna, Emilia-Romagna, Italy

IRCCS Ospedale Policlinico San Martino

Genoa, Liguria, Italy

Istituto Ricerche Farmacologiche Mario Negri IRCCS

Bergamo, Lombardy, Italy

Ospedale San Raffaele s.r.l.

Milan, Lombardy, Italy

IRCCS Centro Cardiologico Monzino S.p.A

Milan, Lombardy, Italy

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, , Poland

FMC-dialyzacne sluzby, s.r.o. - Kosice

Košice, , Slovakia

BIODIAL, spol. s r.o.

Púchov, , Slovakia

Medivasa s.r.o.

Žilina, , Slovakia

Complejo Hospitalario Universitario de Ferrol | Hospital Naval - Unidad de Hipertensión Arterial

Ferrol, A Coruña, Spain

Complejo Hosp. Univ. A Coruña | Endocrinologia y Nutricion

A Coruña, , Spain

Hospital del Mar

Barcelona, , Spain

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, , Spain

Hospital Quirón

Barcelona, , Spain

Hospital Universitario Virgen de las Nieves|Medicina Interna

Granada, , Spain

Hospital Clínico Universitario de Valencia

Valencia, , Spain

Hospital Universitario Dr. Peset

Valencia, , Spain

PTC-Primary care Trial Center

Gothenburg, , Sweden

Clemenstorget Hjärtmottagning

Lund, , Sweden

Akademiska Sjukhuset Njurmottagningen

Uppsala, , Sweden

ClinSmart

Uppsala, , Sweden

Medical center LLC " Fresenius medical care Ukraine"

Cherkasy, , Ukraine

Dnepropetrovsk regional hospital n.a. I. I. Mechnikov

Dnipro, , Ukraine

Private enterprise private production company " Acinus"

Kropyvnytskyi, , Ukraine

Kyiv City Center of Nephrology and Dialysis

Kyiv, , Ukraine

Medical Center of Edelweiss Medics LLC

Kyiv, , Ukraine

Kyiv City Center of Nephrology and Dialysis

Kyiv, , Ukraine

Volyn Regional Clinical Hospital

Lutsk, , Ukraine

Ternopil Regional Clinical Hospital

Ternopil, , Ukraine

Zaporizhzhia Regional Clinical Hospital

Zaporizhzhya, , Ukraine

Countries

Austria; Belgium; Bulgaria; Denmark; Finland; Germany; Israel; Italy; Poland; Slovakia; Spain; Sweden; Ukraine

References

Gansevoort RT, Wheeler DC, Deben FM, Speeckaert M, Thomas D, Berger M, Klein S, Friedrichs F, Paraschin K, Schmieder RE. The soluble guanylate cyclase activator runcaciguat significantly improves albuminuria in patients with chronic kidney disease: a randomized placebo-controlled clinical trial. Nephrol Dial Transplant. 2025 May 30;40(6):1147-1160. doi: 10.1093/ndt/gfae261.

Reference Type: DERIVED

PMID: 39656628 (View on PubMed)

Kraehling JR, Benardeau A, Schomber T, Popp L, Vienenkoetter J, Ellinger-Ziegelbauer H, Pavkovic M, Hartmann E, Siudak K, Freyberger A, Hagelschuer I, Mathar I, Hueser J, Hahn MG, Geiss V, Eitner F, Sandner P. The sGC Activator Runcaciguat Has Kidney Protective Effects and Prevents a Decline of Kidney Function in ZSF1 Rats. Int J Mol Sci. 2023 Aug 25;24(17):13226. doi: 10.3390/ijms241713226.

Reference Type: DERIVED

PMID: 37686032 (View on PubMed)

Related Links

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Other Identifiers

2019-003297-53

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

18748

Identifier Type: -

Identifier Source: org_study_id