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.

Chronic Kidney Disease Clinical Trial

— CONCORD  

Official title:

A Randomized, Double-blind, Placebo-controlled, Multi-center Study to Assess the Safety and Efficacy of Individually Titrated Oral Doses of Runcaciguat in Subjects With Clinical Diagnosis of Chronic Kidney Disease With Diabetes and/or Hypertension and at Least One Cardiovascular Comorbidity

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04507061
• Other study ID #: 18748
• Secondary ID: 2019-003297-53
• Status: Completed
• Phase: Phase 2
• Start date: September 1, 2020
• Est. completion date: April 5, 2022

Study information

• Verified date: March 2023
• Source: Bayer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 243
• Est. completion date: April 5, 2022
• Est. primary completion date: March 8, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years and older

Eligibility

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%;

Related Conditions & MeSH terms

• Chronic Kidney Disease
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

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

Other:
• Placebo
Sham-titrated dose of matching placebo will be administered orally once a day.

Locations

Country	Name	City	State
Austria	Medizinische Universität Innsbruck	Innsbruck
Austria	Klinik Hietzing	Wien
Austria	Klinik Landstraße - Krankenhaus Rudolfstiftung	Wien
Austria	Universitätsklinikum AKH Wien	Wien
Austria	Zentrum f. klinische Studien Dr. Hanusch GmbH	Wien
Belgium	OL Vrouwziekenhuis - Campus Aalst	Aalst
Belgium	Hôpital Erasme/Erasmus Ziekenhuis	Bruxelles - Brussel
Belgium	UZ Gent	Gent
Belgium	UZ Leuven Gasthuisberg	Leuven
Bulgaria	Med Centre Diamedical 2013	Dimitrovgrad
Bulgaria	MHAT Sveta Karidad	Plovdiv
Bulgaria	Multiprofile Hospital for Active Treatment Medline Clinic	Plovdiv
Bulgaria	MHAT Dr. Bratan Shukerov AD	Smolyan
Bulgaria	MC Kalimat	Sofia
Bulgaria	MHAT "Knyaginya Klementina - Sofia"EAD	Sofia
Bulgaria	MCOMH Preventsia-2000	Stara Zagora
Denmark	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
Finland	StudyCor Oy	Jyväskylä
Finland	Diagnos Klaukkalan Lääkäriasema	Klaukkala
Finland	Satucon / Kuopion Työterveys	Kuopio
Finland	Omena Terveys Oy	Seinäjoki
Finland	Turun yliopistollinen keskussairaala	Turku
Germany	Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)	Bad Oeynhausen	Nordrhein-Westfalen
Germany	DaVita Clinical Research Deutschland GmbH	Duesseldorf	Nordrhein-Westfalen
Germany	InnoDiab Forschung GmbH	Essen	Nordrhein-Westfalen
Germany	Medamed Studienambulanz GmbH	Leipzig	Sachsen
Germany	Klinikum der Universität Würzburg	Wuerzburg	Bayern
Israel	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
Italy	Istituto Ricerche Farmacologiche Mario Negri IRCCS	Bergamo	Lombardia
Italy	A.O.U. di Bologna Policlinico S.Orsola Malpighi	Bologna	Emilia-Romagna
Italy	IRCCS Ospedale Policlinico San Martino	Genova	Liguria
Italy	IRCCS Centro Cardiologico Monzino S.p.A	Milano	Lombardia
Italy	Ospedale San Raffaele s.r.l.	Milano	Lombardia
Italy	A.O.U. Luigi Vanvitelli	Napoli	Campania
Poland	Centralny Szpital Kliniczny MSWiA w Warszawie	Warszawa
Slovakia	FMC-dialyzacne sluzby, s.r.o. - Kosice	Kosice
Slovakia	BIODIAL, spol. s r.o.	Puchov
Slovakia	Medivasa s.r.o.	Zilina
Spain	Complejo Hosp. Univ. A Coruña | Endocrinologia y Nutricion	A Coruña
Spain	Ciutat Sanitaria i Universitaria de la Vall d'Hebron	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Quirón	Barcelona
Spain	Complejo Hospitalario Universitario de Ferrol | Hospital Naval - Unidad de Hipertensión Arterial	Ferrol	A Coruña
Spain	Hospital Universitario Virgen de las Nieves|Medicina Interna	Granada
Spain	Hospital Clínico Universitario de Valencia	Valencia
Spain	Hospital Universitario Dr. Peset	Valencia
Sweden	PTC-Primary care Trial Center	Göteborg
Sweden	Clemenstorget Hjärtmottagning	Lund
Sweden	Akademiska Sjukhuset Njurmottagningen	Uppsala
Sweden	ClinSmart	Uppsala
Ukraine	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	Kyiv City Center of Nephrology and Dialysis	Kyiv
Ukraine	Medical Center of Edelweiss Medics LLC	Kyiv
Ukraine	Volyn Regional Clinical Hospital	Lutsk
Ukraine	Ternopil Regional Clinical Hospital	Ternopil
Ukraine	Zaporizhzhia Regional Clinical Hospital	Zaporizhzhya

Sponsors (1)

Lead Sponsor	Collaborator
Bayer

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Number of subjects with treatment emergent adverse event (TEAE)		From first treatment administration up to end of follow up (Day 87±7)
Secondary	Number of subjects with early discontinuations		From first treatment administration up to end of treatment (Day 57±3)

External Links

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