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.

NCT04507061 | Completed Phase 2 DMC

• 2 other identifiers: 187482019-003297-53
• Study Type: interventional
• Target: 243
• Locations: 13 countries
• Sites: 71

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

Outcome Measures

Primary Outcomes (1)

• Mean change in urinary albumin-to-creatinine ratio (UACR) from baseline to the average of multiple time points during treatment

  From baseline up to day 57 (± 3)

Secondary Outcomes (2)

• Number of subjects with treatment emergent adverse event (TEAE)

  From first treatment administration up to end of follow up (Day 87±7)

• Number of subjects with early discontinuations

  From first treatment administration up to end of treatment (Day 57±3)

Study Arms (2)

runcaciguat

EXPERIMENTAL

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.

Drug: runcaciguat

Placebo

PLACEBO COMPARATOR

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.

Other: Placebo

Interventions

runcaciguat DRUG

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

runcaciguat

Placebo OTHER

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

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• History of active inflammatory bowel disease within the last 6 months before randomization;
• Major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, or bowel resection;
• Gastro-intestinal ulcers and/or gastrointestinal or rectal bleeding within last 6 months before randomization;
• Pancreatic injury or pancreatitis within the last 6 months before randomization;
• Non diabetic patients treated with SGLT-2 (SGLT:sodium glucose transport protein) inhibitors;

Sponsors & Collaborators

• Bayer: lead

Study Sites (71)

Medizinische Universität Innsbruck

Innsbruck, 6020, Austria

Location

Klinik Landstraße - Krankenhaus Rudolfstiftung

Vienna, 1030, Austria

Location

Zentrum f. klinische Studien Dr. Hanusch GmbH

Vienna, 1060, Austria

Location

Universitätsklinikum AKH Wien

Vienna, 1090, Austria

Location

Klinik Hietzing

Vienna, 1130, Austria

Location

OL Vrouwziekenhuis - Campus Aalst

Aalst, 9300, Belgium

Location

Hôpital Erasme/Erasmus Ziekenhuis

Bruxelles - Brussel, 1070, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Med Centre Diamedical 2013

Dimitrovgrad, 6400, Bulgaria

Location

Multiprofile Hospital for Active Treatment Medline Clinic

Plovdiv, 4000, Bulgaria

Location

MHAT Sveta Karidad

Plovdiv, 4004, Bulgaria

Location

MHAT Dr. Bratan Shukerov AD

Smolyan, 4700, Bulgaria

Location

MHAT "Knyaginya Klementina - Sofia"EAD

Sofia, 1233, Bulgaria

Location

MC Kalimat

Sofia, 1680, Bulgaria

Location

MCOMH Preventsia-2000

Stara Zagora, 6000, Bulgaria

Location

Region Nordjylland | Aalborg University Hospital - Cardiology Department

Aalborg, 9000, Denmark

Location

Steno Diabetes Center Copenhagen

Herlev, 2730, Denmark

Location

Regionshospitalet Gødstrup

Herning, 7400, Denmark

Location

Holbæk Sygehus

Holbæk, 4300, Denmark

Location

Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme

Kolding, 6000, Denmark

Location

Odense Universitetshospital, Endokrinologisk Afd. M

Odense C, 5000, Denmark

Location

StudyCor Oy

Jyväskylä, 40620, Finland

Location

Diagnos Klaukkalan Lääkäriasema

Klaukkala, 01800, Finland

Location

Satucon / Kuopion Työterveys

Kuopio, 70100, Finland

Location

Omena Terveys Oy

Seinäjoki, 60320, Finland

Location

Turun yliopistollinen keskussairaala

Turku, 20521, Finland

Location

Klinikum der Universität Würzburg

Würzburg, Bavaria, 97080, Germany

Location

Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)

Bad Oeynhausen, North Rhine-Westphalia, 32545, Germany

Location

DaVita Clinical Research Deutschland GmbH

Düsseldorf, North Rhine-Westphalia, 40210, Germany

Location

InnoDiab Forschung GmbH

Essen, North Rhine-Westphalia, 45136, Germany

Location

Medamed Studienambulanz GmbH

Leipzig, Saxony, 04315, Germany

Location

Barzilai Medical Center | Nephrology & Hypertension Dept.

Ashkelon, 7830604, Israel

Location

Lady Davis Carmel Medical Center

Haifa, 3436212, Israel

Location

Edith Wolfson Medical Center

Holon, 5822012, Israel

Location

Hadassah Hebrew University Hospital Ein Kerem

Jerusalem, 9112001, Israel

Location

Health Corporation of Galilee Medical Center

Nahariya, 2210001, Israel

Location

Clalit Health Services Rabin Medical Center-Beilinson Campus

Petah Tikva, 4941492, Israel

Location

Chaim Sheba Medical Center

Ramat Gan, 5262000, Israel

Location

Poriya Medical Center | Nephrology and Hypertension Dept.

Tiberius, 1528001, Israel

Location

A.O.U. Luigi Vanvitelli

Napoli, Campania, 80131, Italy

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

IRCCS Ospedale Policlinico San Martino

Genoa, Liguria, 16132, Italy

Location

Istituto Ricerche Farmacologiche Mario Negri IRCCS

Bergamo, Lombardy, 24020, Italy

Location

Ospedale San Raffaele s.r.l.

Milan, Lombardy, 20132, Italy

Location

IRCCS Centro Cardiologico Monzino S.p.A

Milan, Lombardy, 20138, Italy

Location

Centralny Szpital Kliniczny MSWiA w Warszawie

Warsaw, 02-507, Poland

Location

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

Košice, 040 11, Slovakia

Location

BIODIAL, spol. s r.o.

Púchov, 020 01, Slovakia

Location

Medivasa s.r.o.

Žilina, 01001, Slovakia

Location

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

Ferrol, A Coruña, 15405, Spain

Location

Complejo Hosp. Univ. A Coruña | Endocrinologia y Nutricion

A Coruña, 150006, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Ciutat Sanitaria i Universitaria de la Vall d'Hebron

Barcelona, 08023, Spain

Location

Hospital Quirón

Barcelona, 08023, Spain

Location

Hospital Universitario Virgen de las Nieves|Medicina Interna

Granada, 18014, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

PTC-Primary care Trial Center

Gothenburg, 413 46, Sweden

Location

Clemenstorget Hjärtmottagning

Lund, 222 21, Sweden

Location

Akademiska Sjukhuset Njurmottagningen

Uppsala, 751 85, Sweden

Location

ClinSmart

Uppsala, 752 37, Sweden

Location

Medical center LLC " Fresenius medical care Ukraine"

Cherkasy, 18009, Ukraine

Location

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

Dnipro, 49005, Ukraine

Location

Private enterprise private production company " Acinus"

Kropyvnytskyi, 25006, Ukraine

Location

Kyiv City Center of Nephrology and Dialysis

Kyiv, 01023, Ukraine

Location

Medical Center of Edelweiss Medics LLC

Kyiv, 02002, Ukraine

Location

Kyiv City Center of Nephrology and Dialysis

Kyiv, 02660, Ukraine

Location

Volyn Regional Clinical Hospital

Lutsk, 43005, Ukraine

Location

Ternopil Regional Clinical Hospital

Ternopil, 46002, Ukraine

Location

Zaporizhzhia Regional Clinical Hospital

Zaporizhzhya, 69600, Ukraine

Location

Related Publications (2)

• 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.

  PMID: 39656628 DERIVED

• 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.

  PMID: 37686032 DERIVED

Related Links

• Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

MeSH Terms

Conditions

Renal Insufficiency, Chronic

Interventions

BAY 1101042

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

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

Study Record Dates

• First Submitted: August 6, 2020
• First Posted: August 10, 2020
• Study Start: September 1, 2020
• Primary Completion: March 8, 2022
• Study Completion: April 5, 2022
• Last Updated: April 4, 2023

Record last verified: 2023-03

Locations

UA (9); DK (6); PL (1); SE (4); SL (3); AU (5); ES (8); IL (8); FI (5); DE (5); BU (7); IT (6); BE (4)