Recruitment Complete

Chronic kidney disease, Proteinuria

Bayer Identifier:

19920

ClinicalTrials.gov Identifier:

NCT05196035

EudraCT Number:

2021-002071-19

EU CT Number:

2023-504884-17-00

A study to learn more about how well the study treatment finerenone works, how safe it is, how it moves into, through, and out of the body, and the effects it has on the body when taken with an ACE inhibitor or angiotensin receptor blocker in children with chronic kidney disease and proteinuria

Trial purpose

Researchers are looking for a better way to treat children who have chronic kidney disease (CKD), which is long-term kidney disease, and proteinuria, a condition in which a person´s kidneys leak protein into the urine.

The kidneys filter waste and fluid from the blood to form urine. In children with CKD, the kidney´s filters do not work as well as they should. This can lead to accumulation of waste and fluid in the body and proteinuria. CKD can lead to other medical problems, such as high blood pressure, also known as hypertension. Vice versa, hypertension and proteinuria can also contribute to worsening of CKD. Therefore, the treatment of CKD aims to control blood pressure and proteinuria. There are treatments available for doctors to prescribe to children with CKD and hypertension and/or proteinuria. These include “angiotensin-converting enzyme inhibitors” (ACEI) and “angiotensin receptor blockers” (ARB). Both ACEI and ARB can improve kidney function by helping the renin-angiotensin-aldosterone system (RAAS) to work normally. The RAAS is a system that works with the kidneys to control blood pressure and the balance of fluid and electrolytes in the blood. In people with CKD, the RAAS is often too active, which can stop the kidneys from working properly and cause hypertension and proteinuria. However, ACEI or ARB treatment alone does not work for all patients with CKD as they only target the angiotensin part of the renin-angiotensin-aldosterone system.

The study treatment, finerenone, is expected to help control RAAS overactivation together with an ACEI or ARB.

So, the researchers in this study want to learn more about whether finerenone given in addition to either an ACEI or ARB can help their kidney function.

The main purpose of this study is to learn more about whether finerenone added to either ACEI or ARB can help reduce the amount of protein in the participants’ urine more than a placebo. A placebo looks like a treatment but does not have any medicine in it. Participants will also continue to receive their other medications.

To see how the treatment work, the doctors will take samples of the participants’ urine to measure their protein levels before and during taking treatment and after their last treatment. In addition, blood samples will be taken to monitor kidney function, electrolytes and the amount of finerenone in the blood as well as for other tests.

This study will include children with CKD and proteinuria aged from 6 months up to less than 18 years. The participants will take:
- either finerenone or the placebo, in addition to
- either ACEI or ARB, whichever they take as part of their normal treatment

Two visits are required up to 104 days, to check whether a child can take part in the treatment phase of the study. If participants qualify for the treatment phase, they will then undergo treatment for about 180 days. During this time, they will visit the study site at least 7 times. During these visits, the participants will:
- have their blood pressure, heart rate, temperature, height and weight measured
- have blood and urine samples taken
- have physical examinations
- have their heart examined by an electrocardiogram and echocardiography (a sonogram of the heart)
- answer questions about their medication and whether they have any adverse events , or have their parents or guardians answer
- answer questions about how they are feeling, or have their parents or guardians answer
- answer question about how they like the study medication, or have their parents or guardians answer

The doctors will keep track of any adverse events. An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.

The doctors will check the participants’ health about 30 days after the participants take their last treatment.

Key Participants Requirements

Sex

All

Age

6 - 17 Years

Inclusion Criteria

- Participants must be 6 months to <18 years old at the time when the informed consent/assent is signed
- Participants must have a clinical diagnosis of chronic kidney disease (CKD) at screening which is defined as
-- CKD stages 1-3 (eGFR ≥30 mL/min/1.73m^2) for children ≥1 year to <18 years of age or
-- a serum creatinine ≤ 0.40 mg/dL for infants 6 months to < 1 year of age
and
-- severely increased proteinuria as defined by
--- Urinary protein-to-creatinine ratio (UPCR) of ≥ 0.50 g/g in participants ≥ 2 years with CKD stage 2 and 3 or
--- UPCR ≥ 1.0 g/g for patients < 2 years of age or ≥ 2 years of age and with CKD stage 1
- Participants must have stable kidney function between screening and D0 defined as:
-- For participants with a creatinine of > 0.8 mg/dL at screening: no increase or decrease in eGFR by ≥ 20% at D0
-- For participants with a creatinine of ≤ 0.8 mg/dL at screening: no increase or decrease in creatinine ≥ 0.15 mg/dL at D0.
- Treated with an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at optimized doses defined as maximally tolerable doses within the recommended dose range according to guidelines on blood pressure management, unchanged for at least 30 days prior to screening
- K+ ≤5.0 mmol/L for children ≥2 years of age at both screening and D0, and ≤5.3 mmol/L for children <2 years of age at both screening and D0

Exclusion Criteria

- Planned urological surgery expected to influence renal function
- Children with hemolytic uremic syndrome (HUS) diagnosed ≤6 months prior to screening
- Patients with nephrotic syndrome receiving albumin infusions within the last 6 months prior to screening
- Patients who are candidates for renal transplantation, i.e., a kidney transplantation scheduled within the study time frame
- Renal allograft in place
- Bilateral renal artery stenosis
- Acute kidney injury requiring dialysis within 6 months prior to screening
- Systemic hypertension stage 2 in children ≥1 year of age defined according to guidelines on blood pressure management at screening or randomization
- Systolic blood pressure (SBP) above 110 mmHg in infants 6 months to <1 year of age at screening or randomization
- Systemic hypotension defined as a systolic blood pressure below the 5th percentile for age, sex and height at either screening or randomization but no lower than 80 mmHg (although for some participants the 5th percentile of SBP is < 80 mmHg they must be excluded if their SBP is <80 mmHg)
- Participants with immune-mediated CKD using rituximab, cyclophosphamide, abatacept, or high-dose glucocorticoids, within <6 months prior to screening

Trial summary

Enrollment Goal

219

Trial Dates

March 2022 - May 2027

Phase

Phase II/III

Could I Receive a placebo

Yes

Products

Finerenone, BAY 948862

Accepts Healthy Volunteer

Where to participate

Status	Institution	Location
Completed	Universitätsklinikum Heidelberg	Heidelberg, 69115, Germany
Completed	Universitätsklinikum Hamburg Eppendorf (UKE)	Hamburg, 20246, Germany
Active, not recruiting	Medizinische Hochschule Hannover (MHH)	Hannover, 30625, Germany
Completed	Universitätsklinikum Essen	Essen, 45147, Germany
Active, not recruiting	Universitätsklinikum Münster	Münster, 48149, Germany
Completed	Kindernierenzentrum Bonn	Bonn, 53127, Germany
Completed	Charité / Pädiatrie	Berlin, 13353, Germany
Completed	Great Ormond Street Hospital for Children \| Clinical Research Facility	London, WC1N 3JH, United Kingdom
Active, not recruiting	Nottingham Children's Hospital \| Renal and Urology Unit	Nottingham, NG7 2UH, United Kingdom
Completed	Royal Manchester Children's Hospital \| Clinical Research Facility	Manchester, M13 9WL, United Kingdom
Completed	Royal Hospital for Children \| Glasgow Clinical Research Facility	Glasgow, G51 4TF, United Kingdom
Withdrawn	University Hospital - San Antonio - Pediatric Nephrology	San Antonio, 78207, United States
Active, not recruiting	Cincinnati Children's Hospital Medical Center \| Division of Nephrology and Hypertension	Cincinnati, 45229, United States
Completed	Seattle Children's Hospital - Nephrology	Seattle, 98105, United States
Active, not recruiting	Memorial Transplant Institute - Pediatric Nephrology	Hollywood, 33021, United States
Completed	Children's Mercy Hospital Kansas City - Nephrology	Kansas City, 64108, United States
Completed	OHSU Doernbecher Children's Hospital - Neurology	Portland, 97239, United States
Completed	Lucille Packard Children's Hospital Stanford - Pediatric Nephrology	Palo Alto, 94304, United States
Completed	Cleveland Clinic \| Pediatric Nephrology	Cleveland, 14013, United States
Withdrawn	University of Iowa Health Care Medical Center - Nephrology	Iowa City, 52242, United States
Active, not recruiting	UC San Diego - Altman Clinical and Translational Research Institute (ACTRI) - Linda Vista Clinic	San Diego, 92023, United States
Completed	Eccles Primary Children's Outpatient Services - Nephrology	Salt Lake City, 84113, United States
Completed	The Charlotte R. Bloomberg Children's Center Building - Nephrology	Baltimore, 21287, United States
Withdrawn	Children's Hospital of Philadelphia - Nephrology	Philadelphia, 19104, United States
Withdrawn	Children's National Hospital - Nephrology	Washington, 20010, United States
Completed	CHU Toulouse - Hopital des enfants	Toulouse, 31059, France
Completed	CHU bordeaux - Hopital Pellegrin	Bordeaux, 33076, France
Completed	CHU Lyon - Hopital Femme Mere Enfant - Service de nephrologie-rhumatologie-dermatologie pediatriques	Bron, 69500, France
Completed	CHU Montpellier - Hopital Arnaud de Villeneuve - Service nephrologie pediatrique	Montpellier cedex 5, 34295, France
Active, not recruiting	CHU Strasbourg - Hopital Hautepierre - Service nephrologie pediatrique	Strasbourg, 67200, France
Completed	APHP - Hopital Robert Debre	Paris, 75019, France
Completed	Instytut "Pomnik – Centrum Zdrowia Dziecka"	Warszawa, 04‐730, Poland
Completed	Uniwersytecki Dzieciecy Szpital Kliniczny im. L. Zamenhofa	Bialystok, 15-274, Poland
Completed	Instytut Centrum Zdrowia Matki Polki	Lodz, 93-338, Poland
Completed	Uniwersyteckie Centrum Kliniczne	Gdansk, 80-952, Poland
Completed	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico - Nefrologia e Dialisi Pediatrica, Trapianti di Rene	Milano, 20122, Italy
Completed	IRCCS Istituto Giannina Gaslini - Nefrologia e Trapianto Rene	Genova, 16147, Italy
Completed	Azienda Ospedaliero-Universitaria Di Bologna IRCCS_Policlinico Sant'Orsola - Pediatria	Bologna, 40138, Italy
Completed	Ospedale Pediatrico Bambino Gesù - Nefrologia	Roma, 00165, Italy
Completed	A.O.U. Città della Salute e della Scienza di Torino_Regina Margherita - Nefrologia Pediatrica	Torino, 10126, Italy
Completed	Azienda Ospedaliera Universitaria Meyer IRCCS - Nefrologia e Dialisi	Firenze, 50139, Italy
Completed	Hospital Universitario Virgen Del Rocio S.L. \| Nefrologia pediatrica	Sevilla, 41013, Spain
Completed	Hospital Universitari Vall D Hebron \| Nefrologia pediatrica	Barcelona, 08035, Spain
Completed	Hospital Sant Joan De Deu Barcelona \| Nefrologia pediatrica	Esplugues de LLobregat, 8950, Spain
Active, not recruiting	Hospital Universitario Regional De Malaga \| Nefrologia pediatrica	Málaga, 29010, Spain
Completed	Hospital Universitario 12 De Octubre \| Nefrologia pediatrica	Madrid, 28041, Spain
Completed	Hospital Universitario La Paz \| Nefrologia pediatrica	Madrid, 28046, Spain
Completed	Centre hospitalier universitaire Sainte-Justine \| Cardiology	Montreal, H3T 1C5, Canada
Active, not recruiting	Alberta Children's Hospital \| Nephrology Clinic	Calgary, T3B 6A8, Canada
Completed	UZ Gasthuisberg - Pediatric Nephrology	Leuven, 3000, Belgium
Completed	UZ Gent	GENT, 9000, Belgium
Active, not recruiting	HUDERF / UKZKF	Bruxelles, 1020, Belgium
Completed	CU Saint-Luc/UZ St-Luc	Bruxelles, 1200, Belgium
Completed	CHC Montlégia - Pediatrics	Liège, 4000, Belgium
Completed	Universitair Medisch Centrum Groningen	Groningen, 9713 GZ, Netherlands
Completed	University Medical Center Utrecht	Utrecht, 3584 CX, Netherlands
Active, not recruiting	Instituto Nacional de Pediatría	México, D.F., 4530, Mexico
Active, not recruiting	Sitio Alfredo Chew Wong \| Aguascalientes, Mexico	Aguascalientes, 20124, Mexico
Completed	Instituto Veracruzano en Investigación Clinica SC	Veracruz, 91900, Mexico
Active, not recruiting	Karolinska Universitetssjukhuset - Huddinge - Barnnjurmedicin	Stockholm - Huddinge, 141 86, Sweden
Completed	Skånes Universitetssjukhus - Lund - Barnnefroenheten	Lund, 221 85, Sweden
Completed	Aarhus Universitetshospital - Børn og Unge	Aarhus N, 8200, Denmark
Completed	Odense Universitetshospital - HC Andersen Børne og Ungehospital	Odense, 5000, Denmark
Completed	Rigshospitalet - Børn og Unge	Copenhagen, 2100, Denmark
Active, not recruiting	Wits Vaccines & Infectious Diseases Analytics (VIDA) Research Unit	Soweto, 1862, South Africa
Completed	Všeobecná fakultní nemocnice v Praze	Praha 2, 128 08, Czech Republic
Completed	Fakultní nemocnice Motol a Homolka, Pracoviště MOTOL	Praha 5, 150 06, Czech Republic
Completed	Clalit Health Services Schneider Children's Medical Center	Petach Tikva, 4920235, Israel
Completed	Dana-Dwek Children’s Hospital	Tel Aviv, 6423906, Israel
Completed	Wilf Children's Hospital Shaare Zedek Medical Center	Jerusalem, 9103102, Israel
Completed	Health Corporation of Galilee Medical Center	Nahariya, 2210001, Israel
Completed	Clalit Health \| Soroka Medical Center	Beer Sheva, 8410101, Israel
Completed	Monash Children's Hospital	Clayton, 3168, Australia
Active, not recruiting	Queensland Children’s Hospital	South Brisbane, 4101, Australia
Terminated	Royal Children's Hospital Melbourne	Parkville, 3052, Australia
Active, not recruiting	UMHAT Sveti Georgi	Plovdiv, 4002, Bulgaria
Completed	Unidade Local de Saúde de Santo António, E.P.E	Porto, 4050-651, Portugal
Completed	Unidade Local de Saúde de Coimbra, E.P.E. - Hospital Pediátrico - Serviço de Pediatria Ambulatória - Nefrologia	Coimbra, 3000, Portugal
Completed	Centro de Rehabilitacion Cardiovascular \| San Luis, Argentina	San Luis, D5700CGR, Argentina
Active, not recruiting	Hospital General de Ninos Ricardo Gutierrez \| Pediatric Nephrology Department	Buenos Aires, C1425EFD, Argentina
Completed	Clinica de Nefrologia, Urologia y Enfermedades Cardiovascualares \| Santa Fe, Argentina	Santa Fé, S3000, Argentina
Completed	Instituto Universitario Hospital Italiano de Buenos Aires \| Hospital Italiano de Buenos Aires - Neurology Department	Buenos Aires, C1199ABB, Argentina
Completed	Hospital General de Ninos Pedro de Elizalde \| Nephrology Department	Buenos Aires, C1270, Argentina
Completed	AKH Wien \| Kinder & Jugendheilkunde, Kindernephrologie	Vienna, 6800, Austria
Active, not recruiting	Medizinische Univ Graz \| Kinder & Jugendheilkunde	Graz, 8036, Austria
Completed	Kepler Universitätsklinikum Campus IV	Innsbruck, 6020, Austria
Completed	Uniklinikum Salzburg - Landeskrankenhaus	Vienna, 1090, Austria
Active, not recruiting	Szegedi Tudományegyetem Szent-Györgyi Albert Klinikai Központ	Szeged, 6720, Hungary
Completed	Semmelweis University	Budapest, 1083, Hungary
Completed	Debreceni Egyetem Klinikai Kozpont	Debrecen, 4032, Hungary
Completed	Pecsi Tudomanyegyetem Klinikai Kozpont	Pécs, 7623, Hungary
Completed	Gazi Universitesi Tip Fakultesi	Ankara, 6560, Turkey
Completed	Hacettepe Universitesi Tip Fakultesi	Ankara, 06230, Turkey
Completed	Istanbul Universitesi Cerrahpasa – Cocuk Nefrolojisi	Istanbul, 34098, Turkey
Completed	T.C. Saglik Bakanligi Ankara Bilkent Sehir Hastanesi Noroloji ve Ortopedi Hastanesi Noroloji Bolumu	Ankara, 6800, Turkey
Completed	Marmara University Medical Faculty \| Pediatric Nephrology	Istanbul, 34899, Turkey
Completed	Baskent Universitesi Tip Fakultesi Hastanesi	Ankara, 6490, Turkey
Completed	Istanbul Faculty of Medicine, Department of Internal Medicine, Department of Pediatrics	Istanbul, 34093, Turkey
Completed	Cukurova Univ. Tip. Fak. Balcali Hastanesi	Adana, 01790, Turkey
Active, not recruiting	Children's Hospital of Athens P&A Kyriakou - Pediatric Nephrology Department	Athens, 11526, Greece
Completed	University General Hospital of Heraklion	Heraklion, 71110, Greece
Completed	University General Hospital Of Ioannina-Child Health Sector	Ioannina, 45500, Greece
Active, not recruiting	Ippokratio General Hospital Of Thessaloniki-Pediatric Nephrology Unit, 3rd Department of Paediatrics	Thessaloniki, 54642, Greece
Active, not recruiting	Children's Hospital of Athens Agia Sofia - Pediatric Nephrology Department	Athens, 11527, Greece
Active, not recruiting	Instituto da Crianca e do Adolescente	São Paulo, 05403 000, Brazil
Completed	Santa Casa de Misericórdia de Belo Horizonte	São Paulo, 30150-221, Brazil
Withdrawn	Hospital Infantil Sabará - Instituto PENSI - Pesquisa e Ensino em Saúde Infantil	São Paulo, 01227-200, Brazil
Completed	Hospital Pequeno Principe	Curitiba, 80250-060, Brazil
Completed	Hospital PUC-Campinas \| Centro de Pesquisa Clínica Sao Lucas	São Paulo, 13034-685, Brazil
Completed	Hosp Clínicas Facult. Med. de Ribeirão Preto / USP	Ribeirão Preto, 14051-140, Brazil
Completed	Seoul National University Hospital \| Pediatric Nephrology	Seoul, 03080, South Korea
Completed	Kyungpook National University Hospital \| Pediatric Nephrology	Daegu, 41944, South Korea
Completed	Pusan National University Children's Hospital \| Pediatric Nephrology	Yangsan-si, 50612, South Korea
Completed	Seoul National University Bundang Hospital \| Pediatric Nephrology	Seongnam-si, 13620, South Korea
Completed	Korea University Guro Hospital \| Pediatric Nephrology	Seoul, 08308, South Korea
Completed	Vilnius University Hospital Santaros Klinikos Children‘s Hospital Paediatrics Centre	Vilnius, LT-08406, Lithuania
Completed	Hospital of LT University of Health Sciences Kaunas Clinics	Kaunas, LT-50161, Lithuania
Completed	Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne University Hospital	Lausanne, 1012, Switzerland
Completed	Universitäts-Kinderspital UKBB	Basel, 4031, Switzerland
Completed	Hopital des Enfants HUG	Geneva, 1211, Switzerland
Completed	HUS-Yhtymä, Helsingin yliopistollinen sairaala (HUS) - Uusi lastensairaala, nefrologia	Helsinki, 00290, Finland
Active, not recruiting	Tampere University Hospital, Tampereen yliopistollinen sairaala (TAYS) - Lasten lääketutkimuskeskus PeeTU	Tampere, 33521, Finland
Completed	Turun yliopistollinen keskussairaala	Turku, 20520, Finland
Completed	St. John's National Academy of Health Sciences	Bengaluru, 560034, India
Completed	All India Institute of Medical Sciences (AIIMS) - New Delhi	Delhi, 110029, India
Completed	NRS Medical college	Kolkata, 700014, India
Completed	Mavani Kidney Care	Ahmedabad, 380052, India
Completed	National Taiwan University Hospital	Taipei, 100229, Taiwan
Completed	Taipei Veterans General Hospital	Taipei, 11217, Taiwan
Active, not recruiting	National Cheng Kung University Hospital	Tainan, 704, Taiwan
Active, not recruiting	Chang Gung Memorial Hospital (CGMH) - Kaohsiung Branch	Guishan, 83301, Taiwan
Active, not recruiting	Chang Gung Memorial Hospital at Linkou	Taipei, 10507, Taiwan
Completed	Hospital Tunku Azizah	Wilayah Persekutuan Putrajaya, 50300, Malaysia
Completed	Hospital Selayang	Shah Alam, 68100, Malaysia
Active, not recruiting	Hospital Tuanku Ja'afar	Seremban, 70300, Malaysia
Completed	Hospital Universiti Sains Malaysia	Kelantan, 16150, Malaysia
Completed	Sunway Medical Centre	Subang Jaya, 47500, Malaysia

Primary Outcome

Percent change in Urinary protein-to-creatinine ratio (UPCR) reduction from baseline to day 180+/-7
Percent change from baseline to day 180±7 in UPCR will be calculated.
Time Frame:
From baseline to day 180+/-7

Secondary Outcome

Number participants with treatment emergent adverse events (TEAEs）
Below sub-categories will be considered: a. Serious Treatment Emergent Adverse Events (TEAEs) b. TEAEs and serious TEAEs leading to discontinuation of treatment c. Study drug related TEAEs and serious TEAEs d. TEAEs categorized by severity (mild, moderate, severe) e. TEAEs by maximum intensity f. Number of participants hospitalized with hyperkalemia, g. Number of participants discontinuing due to hyperkalemia, h. Number of participants with hospitalization for worsening of renal function i. Number of participants discontinuing due to worsening of renal function
Time Frame:
From the start of study intervention to last study intervention + 3 days (up to 190 days)
Change in serum potassium levels from baseline to day 180±7
Time Frame:
From baseline to day 180±7
Change in serum creatinine from baseline to day 180±7
Time Frame:
From baseline to day 180±7
Change in eGFR from baseline to day 180±7
Estimated glomerular filtration rate (eGFR)
Time Frame:
From baseline to day 180±7
Change in systolic blood pressure from baseline to day 180±7
Time Frame:
From baseline to day 180±7
UPCR reduction of at least 30% from baseline to day 180+/-7
Proportion of participants at day 180+/-7 with a >=30% reduction in PUCR compared to baseline
Time Frame:
From baseline to day 180±7
Change in UACR from baseline to day 180±7
Urinary albumin-to-creatinine ratio (UACR)
Time Frame:
From baseline to day 180±7
Pharmacokinetics (PK) finerenone Cmax, md
Maximum observed finerenone concentration in plasma after multiple doses.
Time Frame:
Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7
Pharmacokinetics (PK) finerenone AUCτ,md
Area under the curve for finerenone concentration in plasma after multiple doses.
Time Frame:
Pre-dose, post-dose (1.5-5 hours after intake of intervention), up to day 180±7
Taste and texture questionnaire of the pediatric formulation
Time Frame:
On day 30±3 and day 180±7

Trial design

A 6-month multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and PK/PD of an age-and body weight-adjusted oral finerenone regimen, in addition to an ACEI or ARB, for the treatment of children, 6 months to <18 years of age, with chronic kidney disease and proteinuria

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Treatment

Allocation

Randomized

Blinding

Double-blind

Assignment

Parallel

Trial Arms

Additional Information

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.