Clinical trial NCT04507061: 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.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Kidney Disease
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-08-10
Enrollment: 243
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: 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.


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%;

Primary outcomes:
measure: Mean change in urinary albumin-to-creatinine ratio (UACR) from baseline to the average of multiple time points during treatment
timeFrame: From baseline up to day 57 (± 3)
Secondary outcomes:
measure: Number of subjects with treatment emergent adverse event (TEAE)
timeFrame: From first treatment administration up to end of follow up (Day 87±7)
measure: Number of subjects with early discontinuations
timeFrame: From first treatment administration up to end of treatment (Day 57±3)
Other outcomes:
Locations:
city: Innsbruck
country: Austria
facility: Medizinische Universität Innsbruck
city: Wien
country: Austria
facility: Klinik Landstraße - Krankenhaus Rudolfstiftung
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: Aalst
country: Belgium
facility: OL Vrouwziekenhuis - Campus Aalst
city: Bruxelles - Brussel
country: Belgium
facility: Hôpital Erasme/Erasmus Ziekenhuis
city: Gent
country: Belgium
facility: UZ Gent
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Dimitrovgrad
country: Bulgaria
facility: Med Centre Diamedical 2013
city: Plovdiv
country: Bulgaria
facility: Multiprofile Hospital for Active Treatment Medline Clinic
city: Plovdiv
country: Bulgaria
facility: MHAT Sveta Karidad
city: Smolyan
country: Bulgaria
facility: MHAT Dr. Bratan Shukerov AD
city: Sofia
country: Bulgaria
facility: MHAT "Knyaginya Klementina - Sofia"EAD
city: Sofia
country: Bulgaria
facility: MC Kalimat
city: Stara Zagora
country: Bulgaria
facility: MCOMH Preventsia-2000
city: Aalborg
country: Denmark
facility: Region Nordjylland | Aalborg University Hospital - Cardiology Department
city: Herlev
country: Denmark
facility: Steno Diabetes Center Copenhagen
city: Herning
country: Denmark
facility: Regionshospitalet Gødstrup
city: Holbæk
country: Denmark
facility: Holbæk Sygehus
city: Kolding
country: Denmark
facility: Sygehus Lillebaelt | Kolding Sygehus - Medicinske Sygdomme
city: Odense C
country: Denmark
facility: Odense Universitetshospital, Endokrinologisk Afd. M
city: Jyväskylä
country: Finland
facility: StudyCor Oy
city: Klaukkala
country: Finland
facility: Diagnos Klaukkalan Lääkäriasema
city: Kuopio
country: Finland
facility: Satucon / Kuopion Työterveys
city: Seinäjoki
country: Finland
facility: Omena Terveys Oy
city: Turku
country: Finland
facility: Turun yliopistollinen keskussairaala
city: Wuerzburg
country: Germany
facility: Klinikum der Universität Würzburg
state: Bayern
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen (HDZ NRW)
state: Nordrhein-Westfalen
city: Duesseldorf
country: Germany
facility: DaVita Clinical Research Deutschland GmbH
state: Nordrhein-Westfalen
city: Essen
country: Germany
facility: InnoDiab Forschung GmbH
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
facility: Medamed Studienambulanz GmbH
state: Sachsen
city: Ashkelon
country: Israel
facility: Barzilai Medical Center | Nephrology & Hypertension Dept.
city: Haifa
country: Israel
facility: Lady Davis Carmel Medical Center
city: Holon
country: Israel
facility: Edith Wolfson Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Hebrew University Hospital Ein Kerem
city: Nahariya
country: Israel
facility: Health Corporation of Galilee Medical Center
city: Petah Tikva
country: Israel
facility: Clalit Health Services Rabin Medical Center-Beilinson Campus
city: Ramat Gan
country: Israel
facility: Chaim Sheba Medical Center
city: Tiberius
country: Israel
facility: Poriya Medical Center | Nephrology and Hypertension Dept.
city: Napoli
country: Italy
facility: A.O.U. Luigi Vanvitelli
state: Campania
city: Bologna
country: Italy
facility: A.O.U. di Bologna Policlinico S.Orsola Malpighi
state: Emilia-Romagna
city: Genova
country: Italy
facility: IRCCS Ospedale Policlinico San Martino
state: Liguria
city: Bergamo
country: Italy
facility: Istituto Ricerche Farmacologiche Mario Negri IRCCS
state: Lombardia
city: Milano
country: Italy
facility: Ospedale San Raffaele s.r.l.
state: Lombardia
city: Milano
country: Italy
facility: IRCCS Centro Cardiologico Monzino S.p.A
state: Lombardia
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny MSWiA w Warszawie
city: Kosice
country: Slovakia
facility: FMC-dialyzacne sluzby, s.r.o. - Kosice
city: Puchov
country: Slovakia
facility: BIODIAL, spol. s r.o.
city: Zilina
country: Slovakia
facility: Medivasa s.r.o.
city: Ferrol
country: Spain
facility: Complejo Hospitalario Universitario de Ferrol | Hospital Naval - Unidad de Hipertensión Arterial
state: A Coruña
city: A Coruña
country: Spain
facility: Complejo Hosp. Univ. A Coruña | Endocrinologia y Nutricion
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Ciutat Sanitaria i Universitaria de la Vall d'Hebron
city: Barcelona
country: Spain
facility: Hospital Quirón
city: Granada
country: Spain
facility: Hospital Universitario Virgen de las Nieves|Medicina Interna
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Göteborg
country: Sweden
facility: PTC-Primary care Trial Center
city: Lund
country: Sweden
facility: Clemenstorget Hjärtmottagning
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset Njurmottagningen
city: Uppsala
country: Sweden
facility: ClinSmart
city: Cherkasy
country: Ukraine
facility: Medical center LLC " Fresenius medical care Ukraine"
city: Dnipro
country: Ukraine
facility: Dnepropetrovsk regional hospital n.a. I. I. Mechnikov
city: Kropyvnytskyi
country: Ukraine
facility: Private enterprise private production company " Acinus"
city: Kyiv
country: Ukraine
facility: Kyiv City Center of Nephrology and Dialysis
city: Kyiv
country: Ukraine
facility: Medical Center of Edelweiss Medics LLC
city: Kyiv
country: Ukraine
facility: Kyiv City Center of Nephrology and Dialysis
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital
city: Ternopil
country: Ukraine
facility: Ternopil Regional Clinical Hospital
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhia Regional Clinical Hospital
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: